Stanković, Biljana

Link to this page

Authority KeyName Variants
orcid::0000-0002-7571-277X
  • Stanković, Biljana (51)
Projects
Rare Diseases:Molecular Pathophysiology, Diagnostic and Therapeutic Modalities and Social, Ethical and Legal Aspects info:eu-repo/grantAgreement/MESTD/inst-2020/200042/RS//
Strukturalni elementi genoma u modulaciji fenotipa EFS French Blood Institute
European Commission [FP7-200754] European Commission [International Thalassemia Network (ITHANET)] [026539]
European Commission (RD-CONNECT) [FP7-304555] Fondo di ricerca Ateneo, Universita di Trieste, FRA2018
French Ministry of Foreign Affairs [UMR 3427/US 005] Genotyping of the samples was supported by COVID-19 Host Genetics Initiative. It was performed by the Human Genomics Facility of the Genetic Laboratory of the Department of Internal Medicine at Erasmus MC. Computational resources were provided by The Cancer Genomics Cloud, powered by Seven Bridges, a component of the NCI Cancer Research Data Commons (datacommons.cancer.gov), funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN261201400008C and ID/IQ Agreement No. 17X146 under Contract No. HHSN261201500003I.
info:eu-repo/grantAgreement/EC/FP7/241909/EU// Micromorphological, phytochemical and molecular investigations of plants - systematic, ecological and applicative aspects
Immune system plasticity during aging: Immunomodulatory capacity of oestrogens Molecular, biochemical and immunological tumor diagnosis
Clinical significance of dysfunctions of innate and adaptive immunity in immunoinflammatory and immunodeficiency diseases info:eu-repo/grantAgreement/MESTD/inst-2020/200017/RS//
info:eu-repo/grantAgreement/MESTD/inst-2020/200052/RS// info:eu-repo/grantAgreement/MESTD/inst-2020/200135/RS//
Molecular genetic and ecophysiological researches on the protection of autochthonous animal genetic resources, sustaining domestic animals’ welfare, health and reproduction, and safe food production Italian Ministry of Health (IRCCS Burlo Garofolo) [RC 10_2019]
Research Promotion Foundation (Cyprus) [PiDeltaE046_02] Research Promotion Foundation [PiDelta046_02]
This research was funded by the PharmGenHUB Project 101059870, Twinning Western Balkan call: HORIZON-WIDERA-2021-ACCESS-02

Author's Bibliography

Genome-wide association analysis for severe COVID-19 in Serbian population

Zečević, Marko; Kotur, Nikola; Ristivojević, Bojan; Gašić, Vladimir; Zukić, Branka; Pavlović, Sonja; Stanković, Biljana

(Belgrade : Institute of molecular genetics and genetic engineering, 2023)

TY  - CONF
AU  - Zečević, Marko
AU  - Kotur, Nikola
AU  - Ristivojević, Bojan
AU  - Gašić, Vladimir
AU  - Zukić, Branka
AU  - Pavlović, Sonja
AU  - Stanković, Biljana
PY  - 2023
UR  - https://belbi.bg.ac.rs/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2029
AB  - Host genetics, an important contributor to the COVID-19 clinical susceptibility and severity,
currently is the focus of multiple genome-wide association studies (GWAS) in populations
affected by the pandemic. This is the first study from Serbia that performed a GWAS of
COVID-19 outcomes to identify genetic risk markers of disease severity. A group of 128
hospitalized COVID-19 patients from the Serbian population was enrolled in the study.
We conducted a GWAS comparing (1) patients with pneumonia (n = 80) against patients
without pneumonia (n = 48), and (2) severe (n = 34) against mild disease (n = 48) patients,
using a genotyping array followed by imputation of missing genotypes. We have detected
a significant signal associated with COVID-19 related pneumonia at locus 13q21.33, with
a peak residing upstream of the gene KLHL1 (p = 1.91 × 10−8). Our study also replicated
a previously reported COVID-19 risk locus at 3p21.31, identifying lead variants in SACM1L
and LZTFL1 genes suggestively associated with pneumonia (p = 7.54 × 10−6) and
severe COVID-19 (p = 6.88 × 10−7), respectively. Suggestive association with COVID-19
pneumonia has also been observed at chromosomes 5p15.33 (IRX, NDUFS6,MRPL36, p
= 2.81 × 10−6), 5q11.2 (ESM1, p = 6.59 × 10−6), and 9p23 (TYRP1,LURAP1L, p = 8.69 ×
10−6). The genes located in or near the risk loci are expressed in neural or lung tissues, and
have been previously associated with respiratory diseases such as asthma and COVID-19
or reported as differentially expressed in COVID-19 gene expression profiling studies.
Our results revealed novel risk loci for pneumonia and severe COVID-19 disease which
could contribute to a better understanding of the COVID-19 host genetics in different
populations.
PB  - Belgrade : Institute of molecular genetics and genetic engineering
C3  - 4th Belgrade Bioinformatics Conference
T1  - Genome-wide association analysis for severe COVID-19 in Serbian population
EP  - 84
SP  - 84
VL  - 4
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2029
ER  - 
@conference{
author = "Zečević, Marko and Kotur, Nikola and Ristivojević, Bojan and Gašić, Vladimir and Zukić, Branka and Pavlović, Sonja and Stanković, Biljana",
year = "2023",
abstract = "Host genetics, an important contributor to the COVID-19 clinical susceptibility and severity,
currently is the focus of multiple genome-wide association studies (GWAS) in populations
affected by the pandemic. This is the first study from Serbia that performed a GWAS of
COVID-19 outcomes to identify genetic risk markers of disease severity. A group of 128
hospitalized COVID-19 patients from the Serbian population was enrolled in the study.
We conducted a GWAS comparing (1) patients with pneumonia (n = 80) against patients
without pneumonia (n = 48), and (2) severe (n = 34) against mild disease (n = 48) patients,
using a genotyping array followed by imputation of missing genotypes. We have detected
a significant signal associated with COVID-19 related pneumonia at locus 13q21.33, with
a peak residing upstream of the gene KLHL1 (p = 1.91 × 10−8). Our study also replicated
a previously reported COVID-19 risk locus at 3p21.31, identifying lead variants in SACM1L
and LZTFL1 genes suggestively associated with pneumonia (p = 7.54 × 10−6) and
severe COVID-19 (p = 6.88 × 10−7), respectively. Suggestive association with COVID-19
pneumonia has also been observed at chromosomes 5p15.33 (IRX, NDUFS6,MRPL36, p
= 2.81 × 10−6), 5q11.2 (ESM1, p = 6.59 × 10−6), and 9p23 (TYRP1,LURAP1L, p = 8.69 ×
10−6). The genes located in or near the risk loci are expressed in neural or lung tissues, and
have been previously associated with respiratory diseases such as asthma and COVID-19
or reported as differentially expressed in COVID-19 gene expression profiling studies.
Our results revealed novel risk loci for pneumonia and severe COVID-19 disease which
could contribute to a better understanding of the COVID-19 host genetics in different
populations.",
publisher = "Belgrade : Institute of molecular genetics and genetic engineering",
journal = "4th Belgrade Bioinformatics Conference",
title = "Genome-wide association analysis for severe COVID-19 in Serbian population",
pages = "84-84",
volume = "4",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2029"
}
Zečević, M., Kotur, N., Ristivojević, B., Gašić, V., Zukić, B., Pavlović, S.,& Stanković, B.. (2023). Genome-wide association analysis for severe COVID-19 in Serbian population. in 4th Belgrade Bioinformatics Conference
Belgrade : Institute of molecular genetics and genetic engineering., 4, 84-84.
https://hdl.handle.net/21.15107/rcub_imagine_2029
Zečević M, Kotur N, Ristivojević B, Gašić V, Zukić B, Pavlović S, Stanković B. Genome-wide association analysis for severe COVID-19 in Serbian population. in 4th Belgrade Bioinformatics Conference. 2023;4:84-84.
https://hdl.handle.net/21.15107/rcub_imagine_2029 .
Zečević, Marko, Kotur, Nikola, Ristivojević, Bojan, Gašić, Vladimir, Zukić, Branka, Pavlović, Sonja, Stanković, Biljana, "Genome-wide association analysis for severe COVID-19 in Serbian population" in 4th Belgrade Bioinformatics Conference, 4 (2023):84-84,
https://hdl.handle.net/21.15107/rcub_imagine_2029 .

NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia

Ristivojević, Bojan; Kotur, Nikola; Tošić, Nataša; Stanković, Biljana; Gašić, Vladimir; Pavlović, Đorđe; Jelovac, Marina; Milošević, Goran; Pavlović, Sonja; Zukić, Branka

(Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade, 2023)

TY  - CONF
AU  - Ristivojević, Bojan
AU  - Kotur, Nikola
AU  - Tošić, Nataša
AU  - Stanković, Biljana
AU  - Gašić, Vladimir
AU  - Pavlović, Đorđe
AU  - Jelovac, Marina
AU  - Milošević, Goran
AU  - Pavlović, Sonja
AU  - Zukić, Branka
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2128
AB  - Introduction: The NUDT15 is new pharmacogene of importance for 6-mercaptopurine therapy, given to
children with acute lymphoblastic leukemia (ALL). The association ofside effectsin children with variants
in NUDT15 are well established in Asian populations, yet the relevance ofthis pharmacogene in European
populationsremainslargely unexplored. The aim of thisstudy wasto identify pharmacogenetic variants
in coding and neighbouring regions of NUDT15 gene and analyse if the expression levels of NUDT15 can
predict the occurence of side effects of 6-mercaptopurine during the maintenance therapy in children
with ALL of Serbian origin.
Methods: The genotyping of coding and neighbouring regions of NUDT15 gene was performed using
PCR and Sangersequencing based technology in 48 children with ALL. NUDT15 expression was analyzed
in mononuclear cells of 24 ALL patients at diagnosis and 6 healthy controls by qRT-PCR, and association
with surogate markers was assessed using adequate statistical methodology.
Results: The genotypig revealed the presence of 5 variantsin NUDT15 (NUDT15(NM_018283.4):c.36A>C,
NUDT15(NM_018283.4):c.158+117C>T,NUDT15(NM_018283.4):c.158+174G>A,NUDT15(NM_018283.4):c.159-
91G>A,NUDT15(NM_018283.4):c.*7G>A), none of them with effects on the expression or the function of
NUDT15 protein. There was no statistically significant association between the expression of NUDT15 at
diagnosis and the surogate markers of side effects (number of episodes of leukopenia (p=0.821), number of weeks without therapy (p=0.507), number of weeks with lower dose (p=0.434), average doses
(p=0.374)) of 6-mercaptopurine during the maintenance therapy.
Conclusion: Presently, NUDT15 cannot be used as a pharmacogene in predicting the toxicity of 6-mercaptopurine terapy in children with ALL in Serbia.
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia
EP  - 81
SP  - 81
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2128
ER  - 
@conference{
author = "Ristivojević, Bojan and Kotur, Nikola and Tošić, Nataša and Stanković, Biljana and Gašić, Vladimir and Pavlović, Đorđe and Jelovac, Marina and Milošević, Goran and Pavlović, Sonja and Zukić, Branka",
year = "2023",
abstract = "Introduction: The NUDT15 is new pharmacogene of importance for 6-mercaptopurine therapy, given to
children with acute lymphoblastic leukemia (ALL). The association ofside effectsin children with variants
in NUDT15 are well established in Asian populations, yet the relevance ofthis pharmacogene in European
populationsremainslargely unexplored. The aim of thisstudy wasto identify pharmacogenetic variants
in coding and neighbouring regions of NUDT15 gene and analyse if the expression levels of NUDT15 can
predict the occurence of side effects of 6-mercaptopurine during the maintenance therapy in children
with ALL of Serbian origin.
Methods: The genotyping of coding and neighbouring regions of NUDT15 gene was performed using
PCR and Sangersequencing based technology in 48 children with ALL. NUDT15 expression was analyzed
in mononuclear cells of 24 ALL patients at diagnosis and 6 healthy controls by qRT-PCR, and association
with surogate markers was assessed using adequate statistical methodology.
Results: The genotypig revealed the presence of 5 variantsin NUDT15 (NUDT15(NM_018283.4):c.36A>C,
NUDT15(NM_018283.4):c.158+117C>T,NUDT15(NM_018283.4):c.158+174G>A,NUDT15(NM_018283.4):c.159-
91G>A,NUDT15(NM_018283.4):c.*7G>A), none of them with effects on the expression or the function of
NUDT15 protein. There was no statistically significant association between the expression of NUDT15 at
diagnosis and the surogate markers of side effects (number of episodes of leukopenia (p=0.821), number of weeks without therapy (p=0.507), number of weeks with lower dose (p=0.434), average doses
(p=0.374)) of 6-mercaptopurine during the maintenance therapy.
Conclusion: Presently, NUDT15 cannot be used as a pharmacogene in predicting the toxicity of 6-mercaptopurine terapy in children with ALL in Serbia.",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia",
pages = "81-81",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2128"
}
Ristivojević, B., Kotur, N., Tošić, N., Stanković, B., Gašić, V., Pavlović, Đ., Jelovac, M., Milošević, G., Pavlović, S.,& Zukić, B.. (2023). NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 81-81.
https://hdl.handle.net/21.15107/rcub_imagine_2128
Ristivojević B, Kotur N, Tošić N, Stanković B, Gašić V, Pavlović Đ, Jelovac M, Milošević G, Pavlović S, Zukić B. NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:81-81.
https://hdl.handle.net/21.15107/rcub_imagine_2128 .
Ristivojević, Bojan, Kotur, Nikola, Tošić, Nataša, Stanković, Biljana, Gašić, Vladimir, Pavlović, Đorđe, Jelovac, Marina, Milošević, Goran, Pavlović, Sonja, Zukić, Branka, "NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):81-81,
https://hdl.handle.net/21.15107/rcub_imagine_2128 .

Micronutrients, genetics and COVID-19

Kotur, Nikola; Stanković, Biljana; Pavlović, Sonja

(2023)

TY  - JOUR
AU  - Kotur, Nikola
AU  - Stanković, Biljana
AU  - Pavlović, Sonja
PY  - 2023
UR  - https://journals.lww.com/co-clinicalnutrition/Abstract/2023/07000/Micronutrients,_genetics_and_COVID_19.3.aspx#ContentAccessOptions
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1907
AB  - Purpose of review Marked inter-individual differences in the clinical manifestation of coronavirus disease 2019 (COVID-19) disease has initiated studies in the field of genetics. This review evaluates recent genetic evidence (predominantly in the last 18 months) related to micronutrients (vitamins and trace elements) and COVID-19. Recent findings  AQ5 In patients infected with SARS-CoV-2 virus, altered circulating levels of micronutrients may serve as prognostic markers of disease severity. Mendelian randomization (MR) studies did not find significant effect of variable genetically predicted levels of micronutrients on COVID-19 phenotypes, however, recent clinical studies on COVID-19 point out to vitamin D and zinc supplementation as a nutritional strategy to reduce disease severity and mortality. Recent evidence also points to variants in vitamin D receptor (VDR) gene, most notably rs2228570 (FokI) ‘‘f’’ allele and rs7975232 (ApaI) ‘‘aa’’ genotype as poor prognostic markers. Summary Since several micronutrients were included in the COVID-19 therapy protocols, research in the field of nutrigenetics of micronutrients is in progress. Recent findings from MR studies prioritize genes involved in biological effect, such as the VDR gene, rather than micronutrient status in future research. Emerging evidence on nutrigenetic markers may improve patient stratification and inform nutritional strategies against severe COVID-19.
T2  - Current Opinion in Clinical Nutrition & Metabolic Care
T2  - Current Opinion in Clinical Nutrition & Metabolic Care
T1  - Micronutrients, genetics and COVID-19
EP  - 315
IS  - 4
SP  - 309
VL  - 26
DO  - 10.1097/MCO.0000000000000942
ER  - 
@article{
author = "Kotur, Nikola and Stanković, Biljana and Pavlović, Sonja",
year = "2023",
abstract = "Purpose of review Marked inter-individual differences in the clinical manifestation of coronavirus disease 2019 (COVID-19) disease has initiated studies in the field of genetics. This review evaluates recent genetic evidence (predominantly in the last 18 months) related to micronutrients (vitamins and trace elements) and COVID-19. Recent findings  AQ5 In patients infected with SARS-CoV-2 virus, altered circulating levels of micronutrients may serve as prognostic markers of disease severity. Mendelian randomization (MR) studies did not find significant effect of variable genetically predicted levels of micronutrients on COVID-19 phenotypes, however, recent clinical studies on COVID-19 point out to vitamin D and zinc supplementation as a nutritional strategy to reduce disease severity and mortality. Recent evidence also points to variants in vitamin D receptor (VDR) gene, most notably rs2228570 (FokI) ‘‘f’’ allele and rs7975232 (ApaI) ‘‘aa’’ genotype as poor prognostic markers. Summary Since several micronutrients were included in the COVID-19 therapy protocols, research in the field of nutrigenetics of micronutrients is in progress. Recent findings from MR studies prioritize genes involved in biological effect, such as the VDR gene, rather than micronutrient status in future research. Emerging evidence on nutrigenetic markers may improve patient stratification and inform nutritional strategies against severe COVID-19.",
journal = "Current Opinion in Clinical Nutrition & Metabolic Care, Current Opinion in Clinical Nutrition & Metabolic Care",
title = "Micronutrients, genetics and COVID-19",
pages = "315-309",
number = "4",
volume = "26",
doi = "10.1097/MCO.0000000000000942"
}
Kotur, N., Stanković, B.,& Pavlović, S.. (2023). Micronutrients, genetics and COVID-19. in Current Opinion in Clinical Nutrition & Metabolic Care, 26(4), 309-315.
https://doi.org/10.1097/MCO.0000000000000942
Kotur N, Stanković B, Pavlović S. Micronutrients, genetics and COVID-19. in Current Opinion in Clinical Nutrition & Metabolic Care. 2023;26(4):309-315.
doi:10.1097/MCO.0000000000000942 .
Kotur, Nikola, Stanković, Biljana, Pavlović, Sonja, "Micronutrients, genetics and COVID-19" in Current Opinion in Clinical Nutrition & Metabolic Care, 26, no. 4 (2023):309-315,
https://doi.org/10.1097/MCO.0000000000000942 . .
1

In Silico analysis and prediction of novel pharmacogenomic markers of pediatric ALL treatment

Gašić, Vladimir; Kotur, Nikola; Stanković, Biljana; Pavlović, Đorđe; Jelovac, Marina; Perić, Jelena; Ristivojević, Bojan; Pavlović, Sonja; Zukić, Branka

(Belgrade : Institute of molecular genetics and genetic engineering, 2023)

TY  - CONF
AU  - Gašić, Vladimir
AU  - Kotur, Nikola
AU  - Stanković, Biljana
AU  - Pavlović, Đorđe
AU  - Jelovac, Marina
AU  - Perić, Jelena
AU  - Ristivojević, Bojan
AU  - Pavlović, Sonja
AU  - Zukić, Branka
PY  - 2023
UR  - https://belbi.bg.ac.rs/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2040
AB  - Acute lymphoblastic leukemia (ALL) is the most common childhood neoplasm. Side
effects of therapy occur in 75% of patients and 1-3% of patients have a lethal outcome due
to treatment. More efficient treatment of pediatric ALL has been developed by avoiding
drug adverse effects included in the treatment protocols. Therefore, implementation of
pharmacogenomics is paramount in pediatric ALL treatment. Next generation sequencing
(NGS) contributed to discovery of novel genetic markers, potential candidates for targeted
therapy and predictors of efficacy and toxicity of drugs.
We aimed to discover novel potential pharmacogenomic markers in pediatric ALL.
DNA samples from bone marrow of 17 pediatric ALL patients were analyzed using
the platform TruSeq Amplicon – Cancer Panel (Ilumina) for somatic mutations in 48
oncogenes. DNA samples from blood of 100 individuals, using the platform TruSightOne
(Ilumina), were analyzed for germinative mutations. An in-house virtual panel for GC
response markers was designed. Predicting the effects of novel variants was performed
using the SIFT, PolyPhen-2 and PROVEAN software tools. For protein structure stability
and modeling we used STRUM method and i-TASSER server.
In the NGS study of somatic mutations in pediatric ALL, 9 novel variants have been
identified. Bioinformatic analysis has shown that STK11 c.1023G>T and ERBB2 c.2341C>T
possess potential as pharmacogenomic markers, therefore, they are candidates for
molecular targeted therapy. In the exome sequencing study, according to the prediction
algorithms, 3 new potential markers in pharmacogenes related to GC response have been
identified, ABCB1 c.947A>G, NCOA3 rs138733364 and TBX21 rs14059812.
Using NGS analysis and prediction algorithms, we have detected 2 novel somatic mutations,
candidates for targeted molecular therapy, as well as 3 novel germinative variants,
potential pharmacogenomic markers of GC response in pediatric ALL. Pharmacogenomic
profiling of each pediatric ALL patient is indispensable for new therapy approaches and it
could lead to better outcomes.
PB  - Belgrade : Institute of molecular genetics and genetic engineering
C3  - 4th Belgrade Bioinformatics Conference
T1  - In Silico analysis and prediction of novel pharmacogenomic markers of pediatric ALL treatment
EP  - 95
SP  - 95
VL  - 4
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2040
ER  - 
@conference{
author = "Gašić, Vladimir and Kotur, Nikola and Stanković, Biljana and Pavlović, Đorđe and Jelovac, Marina and Perić, Jelena and Ristivojević, Bojan and Pavlović, Sonja and Zukić, Branka",
year = "2023",
abstract = "Acute lymphoblastic leukemia (ALL) is the most common childhood neoplasm. Side
effects of therapy occur in 75% of patients and 1-3% of patients have a lethal outcome due
to treatment. More efficient treatment of pediatric ALL has been developed by avoiding
drug adverse effects included in the treatment protocols. Therefore, implementation of
pharmacogenomics is paramount in pediatric ALL treatment. Next generation sequencing
(NGS) contributed to discovery of novel genetic markers, potential candidates for targeted
therapy and predictors of efficacy and toxicity of drugs.
We aimed to discover novel potential pharmacogenomic markers in pediatric ALL.
DNA samples from bone marrow of 17 pediatric ALL patients were analyzed using
the platform TruSeq Amplicon – Cancer Panel (Ilumina) for somatic mutations in 48
oncogenes. DNA samples from blood of 100 individuals, using the platform TruSightOne
(Ilumina), were analyzed for germinative mutations. An in-house virtual panel for GC
response markers was designed. Predicting the effects of novel variants was performed
using the SIFT, PolyPhen-2 and PROVEAN software tools. For protein structure stability
and modeling we used STRUM method and i-TASSER server.
In the NGS study of somatic mutations in pediatric ALL, 9 novel variants have been
identified. Bioinformatic analysis has shown that STK11 c.1023G>T and ERBB2 c.2341C>T
possess potential as pharmacogenomic markers, therefore, they are candidates for
molecular targeted therapy. In the exome sequencing study, according to the prediction
algorithms, 3 new potential markers in pharmacogenes related to GC response have been
identified, ABCB1 c.947A>G, NCOA3 rs138733364 and TBX21 rs14059812.
Using NGS analysis and prediction algorithms, we have detected 2 novel somatic mutations,
candidates for targeted molecular therapy, as well as 3 novel germinative variants,
potential pharmacogenomic markers of GC response in pediatric ALL. Pharmacogenomic
profiling of each pediatric ALL patient is indispensable for new therapy approaches and it
could lead to better outcomes.",
publisher = "Belgrade : Institute of molecular genetics and genetic engineering",
journal = "4th Belgrade Bioinformatics Conference",
title = "In Silico analysis and prediction of novel pharmacogenomic markers of pediatric ALL treatment",
pages = "95-95",
volume = "4",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2040"
}
Gašić, V., Kotur, N., Stanković, B., Pavlović, Đ., Jelovac, M., Perić, J., Ristivojević, B., Pavlović, S.,& Zukić, B.. (2023). In Silico analysis and prediction of novel pharmacogenomic markers of pediatric ALL treatment. in 4th Belgrade Bioinformatics Conference
Belgrade : Institute of molecular genetics and genetic engineering., 4, 95-95.
https://hdl.handle.net/21.15107/rcub_imagine_2040
Gašić V, Kotur N, Stanković B, Pavlović Đ, Jelovac M, Perić J, Ristivojević B, Pavlović S, Zukić B. In Silico analysis and prediction of novel pharmacogenomic markers of pediatric ALL treatment. in 4th Belgrade Bioinformatics Conference. 2023;4:95-95.
https://hdl.handle.net/21.15107/rcub_imagine_2040 .
Gašić, Vladimir, Kotur, Nikola, Stanković, Biljana, Pavlović, Đorđe, Jelovac, Marina, Perić, Jelena, Ristivojević, Bojan, Pavlović, Sonja, Zukić, Branka, "In Silico analysis and prediction of novel pharmacogenomic markers of pediatric ALL treatment" in 4th Belgrade Bioinformatics Conference, 4 (2023):95-95,
https://hdl.handle.net/21.15107/rcub_imagine_2040 .

Covid-19 disease severity associated with vitamin d related genetic Variants

Kotur, Nikola; Skakić, Anita; Klaassen, Kristel; Gašić, Vladimir; Jelovac, Marina; Ristivojević, Bojan; Zukić, Branka; Pavlović, Sonja; Stanković, Biljana

(Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo, 2023)

TY  - CONF
AU  - Kotur, Nikola
AU  - Skakić, Anita
AU  - Klaassen, Kristel
AU  - Gašić, Vladimir
AU  - Jelovac, Marina
AU  - Ristivojević, Bojan
AU  - Zukić, Branka
AU  - Pavlović, Sonja
AU  - Stanković, Biljana
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1904
AB  - COVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The
emerging amount of data indicates that vitamin D could be important for clinical presentation of
COVID-19. Here, we investigated association of genetic variants related to the altered level and
bioavailability of vitamin D with clinical severity of COVID-19. We analyzed variants in genes
significant for the status of vitamin D (DHCR7/NADSYN1 rs12785878, GC rs2282679, and CYP2R1
rs10741657), and vitamin D effect (VDR rs2228570) in 120 Serbian adult and pediatric COVID-19
patients using allelic discrimination. Furthermore, we carried out comparative population genetic
analysis among European and other worldwide populations to investigate variation in allelic
frequencies of selected variants. The results showed that DHCR7/NADSYN rs12785878 and CYP2R1
rs10741657 variants were associated with severe COVID-19 in adults (p = 0.03, p = 0.017,
respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the
odds for developing severe disease, OR 0.21 (0.05–0.9) and OR 5.9 (1.4–25.2), respectively. There
were no associations between selected genetic variants and disease severity in pediatric patients.
Comparative population genetic analysis revealed that Serbian population had the lowest frequency of
CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and
0.66 in Spanish and Italian population, respectively), suggesting that other populations should also
investigate the relationship of CYP2R1 variant and the COVID-19 disease course. The results of the
study indicated that vitamin D related genetic variants were implicated in severe COVID-19 in adults.
This could direct prevention strategies based on population specific nutrigenetic profiles.
PB  - Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo
C3  - Genetics & Applications
T1  - Covid-19 disease severity associated with vitamin d related genetic Variants
IS  - 2 (Special edition
SP  - 144
VL  - 7
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1904
ER  - 
@conference{
author = "Kotur, Nikola and Skakić, Anita and Klaassen, Kristel and Gašić, Vladimir and Jelovac, Marina and Ristivojević, Bojan and Zukić, Branka and Pavlović, Sonja and Stanković, Biljana",
year = "2023",
abstract = "COVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The
emerging amount of data indicates that vitamin D could be important for clinical presentation of
COVID-19. Here, we investigated association of genetic variants related to the altered level and
bioavailability of vitamin D with clinical severity of COVID-19. We analyzed variants in genes
significant for the status of vitamin D (DHCR7/NADSYN1 rs12785878, GC rs2282679, and CYP2R1
rs10741657), and vitamin D effect (VDR rs2228570) in 120 Serbian adult and pediatric COVID-19
patients using allelic discrimination. Furthermore, we carried out comparative population genetic
analysis among European and other worldwide populations to investigate variation in allelic
frequencies of selected variants. The results showed that DHCR7/NADSYN rs12785878 and CYP2R1
rs10741657 variants were associated with severe COVID-19 in adults (p = 0.03, p = 0.017,
respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the
odds for developing severe disease, OR 0.21 (0.05–0.9) and OR 5.9 (1.4–25.2), respectively. There
were no associations between selected genetic variants and disease severity in pediatric patients.
Comparative population genetic analysis revealed that Serbian population had the lowest frequency of
CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and
0.66 in Spanish and Italian population, respectively), suggesting that other populations should also
investigate the relationship of CYP2R1 variant and the COVID-19 disease course. The results of the
study indicated that vitamin D related genetic variants were implicated in severe COVID-19 in adults.
This could direct prevention strategies based on population specific nutrigenetic profiles.",
publisher = "Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo",
journal = "Genetics & Applications",
title = "Covid-19 disease severity associated with vitamin d related genetic Variants",
number = "2 (Special edition",
pages = "144",
volume = "7",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1904"
}
Kotur, N., Skakić, A., Klaassen, K., Gašić, V., Jelovac, M., Ristivojević, B., Zukić, B., Pavlović, S.,& Stanković, B.. (2023). Covid-19 disease severity associated with vitamin d related genetic Variants. in Genetics & Applications
Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo., 7(2 (Special edition), 144.
https://hdl.handle.net/21.15107/rcub_imagine_1904
Kotur N, Skakić A, Klaassen K, Gašić V, Jelovac M, Ristivojević B, Zukić B, Pavlović S, Stanković B. Covid-19 disease severity associated with vitamin d related genetic Variants. in Genetics & Applications. 2023;7(2 (Special edition):144.
https://hdl.handle.net/21.15107/rcub_imagine_1904 .
Kotur, Nikola, Skakić, Anita, Klaassen, Kristel, Gašić, Vladimir, Jelovac, Marina, Ristivojević, Bojan, Zukić, Branka, Pavlović, Sonja, Stanković, Biljana, "Covid-19 disease severity associated with vitamin d related genetic Variants" in Genetics & Applications, 7, no. 2 (Special edition (2023):144,
https://hdl.handle.net/21.15107/rcub_imagine_1904 .

The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia

Ristivojević, Bojan; Kotur, Nikola; Stanković, Biljana; Gašić, Vladimir; Pavlović, Đorđe; Jelovac, Marina; Pavlović, Sonja; Zukić, Branka

(Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo, 2023)

TY  - CONF
AU  - Ristivojević, Bojan
AU  - Kotur, Nikola
AU  - Stanković, Biljana
AU  - Gašić, Vladimir
AU  - Pavlović, Đorđe
AU  - Jelovac, Marina
AU  - Pavlović, Sonja
AU  - Zukić, Branka
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1902
AB  - Vincristine (VCR) is one of the key drugs in current treatment protocols for pediatric acute
lymphoblastic leukemia (ALL). By destabilization of microtubules, VCR arrests cells in metaphase,
inducing apoptosis of malignant cells. VCR also causes axonal degradation and impairment of axonal
transport, which leads to vincristine-induced peripheral neuropathy (VIPN). The aim of this study was
to determine if the selected genetic variants are associated with the development of VIPN in ALL
children treated with VCR in Serbia. This study also aimed to discover candidate pharmacogenomic
markers of VIPN in Serbian population. PCR and sequencing-based methodology was used to detect
variants in following genes: CYP3А5 (rs776746), CEP72 (rs924607), ACTG1 (rs1135989), MIR3117
(rs12402181) and MIR4481 (rs7896283). Statistical analyses were performed for investigation of their
association with VIPN in 56 pediatric ALL patients. Population VCR pharmacogenomics analysis of 17
pharmacogenes from in-house next-generation sequencing data was also done. Data on allele frequency
distribution for European population were extracted from public databases. During the treatment,
17.86% of patients developed VIPN. Association analyses have shown that none of the investigated
genetic variants contributed to the occurrence of VIPN in our study group. Population
pharmacogenomics study didn’t reveal valid candidate pharmacovariants for the occurrence of VIPN.
Our results suggested that pre-emptive pharmacogenetic testing for VCR is not applicable. More
comprehensive approaches are needed to identify panel of genes that could explain the VIPN
development after VCR administration in ALL patients. Utilizing better designed GWAS studies and
more robust artificial intelligence-based tools would provide a panel of pharmacogenes for pre-emptive
tests of VIPN to individualize therapy for ALL in children.
PB  - Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo
C3  - Genetics & Applications
T1  - The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia
IS  - 2 (Special edition)
SP  - 109
VL  - 7
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1902
ER  - 
@conference{
author = "Ristivojević, Bojan and Kotur, Nikola and Stanković, Biljana and Gašić, Vladimir and Pavlović, Đorđe and Jelovac, Marina and Pavlović, Sonja and Zukić, Branka",
year = "2023",
abstract = "Vincristine (VCR) is one of the key drugs in current treatment protocols for pediatric acute
lymphoblastic leukemia (ALL). By destabilization of microtubules, VCR arrests cells in metaphase,
inducing apoptosis of malignant cells. VCR also causes axonal degradation and impairment of axonal
transport, which leads to vincristine-induced peripheral neuropathy (VIPN). The aim of this study was
to determine if the selected genetic variants are associated with the development of VIPN in ALL
children treated with VCR in Serbia. This study also aimed to discover candidate pharmacogenomic
markers of VIPN in Serbian population. PCR and sequencing-based methodology was used to detect
variants in following genes: CYP3А5 (rs776746), CEP72 (rs924607), ACTG1 (rs1135989), MIR3117
(rs12402181) and MIR4481 (rs7896283). Statistical analyses were performed for investigation of their
association with VIPN in 56 pediatric ALL patients. Population VCR pharmacogenomics analysis of 17
pharmacogenes from in-house next-generation sequencing data was also done. Data on allele frequency
distribution for European population were extracted from public databases. During the treatment,
17.86% of patients developed VIPN. Association analyses have shown that none of the investigated
genetic variants contributed to the occurrence of VIPN in our study group. Population
pharmacogenomics study didn’t reveal valid candidate pharmacovariants for the occurrence of VIPN.
Our results suggested that pre-emptive pharmacogenetic testing for VCR is not applicable. More
comprehensive approaches are needed to identify panel of genes that could explain the VIPN
development after VCR administration in ALL patients. Utilizing better designed GWAS studies and
more robust artificial intelligence-based tools would provide a panel of pharmacogenes for pre-emptive
tests of VIPN to individualize therapy for ALL in children.",
publisher = "Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo",
journal = "Genetics & Applications",
title = "The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia",
number = "2 (Special edition)",
pages = "109",
volume = "7",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1902"
}
Ristivojević, B., Kotur, N., Stanković, B., Gašić, V., Pavlović, Đ., Jelovac, M., Pavlović, S.,& Zukić, B.. (2023). The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia. in Genetics & Applications
Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo., 7(2 (Special edition)), 109.
https://hdl.handle.net/21.15107/rcub_imagine_1902
Ristivojević B, Kotur N, Stanković B, Gašić V, Pavlović Đ, Jelovac M, Pavlović S, Zukić B. The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia. in Genetics & Applications. 2023;7(2 (Special edition)):109.
https://hdl.handle.net/21.15107/rcub_imagine_1902 .
Ristivojević, Bojan, Kotur, Nikola, Stanković, Biljana, Gašić, Vladimir, Pavlović, Đorđe, Jelovac, Marina, Pavlović, Sonja, Zukić, Branka, "The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia" in Genetics & Applications, 7, no. 2 (Special edition) (2023):109,
https://hdl.handle.net/21.15107/rcub_imagine_1902 .

Genetic Aspects of Micronutrients Important for Inflammatory Bowel Disease

Dragasevic, Sanja; Stanković, Biljana; Kotur, Nikola; Milutinovic, Aleksandra Sokic; Milovanovic, Tamara; Stojkovic Lalosevic, Milica; Stojanovic, Maja; Pavlović, Sonja; Popovic, Dragan

(2022)

TY  - JOUR
AU  - Dragasevic, Sanja
AU  - Stanković, Biljana
AU  - Kotur, Nikola
AU  - Milutinovic, Aleksandra Sokic
AU  - Milovanovic, Tamara
AU  - Stojkovic Lalosevic, Milica
AU  - Stojanovic, Maja
AU  - Pavlović, Sonja
AU  - Popovic, Dragan
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1664
AB  - Inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) are complex diseases whose etiology is associated with genetic and environmental risk factors, among which are diet and gut microbiota. To date, IBD is an incurable disease and the main goal of its treatment is to reduce symptoms, prevent complications, and improve nutritional status and the quality of life. Patients with IBD usually suffer from nutritional deficiency with imbalances of specific micronutrient levels that contribute to the further deterioration of the disease. Therefore, along with medications usually used for IBD treatment, therapeutic strategies also include the supplementation of micronutrients such as vitamin D, folic acid, iron, and zinc. Micronutrient supplementation tailored according to individual needs could help patients to maintain overall health, avoid the triggering of symptoms, and support remission. The identification of individuals’ genotypes associated with the absorption, transport and metabolism of micronutrients can modify future clinical practice in IBD and enable individualized treatment. This review discusses the personalized approach with respect to genetics related to micronutrients commonly used in inflammatory bowel disease treatment.
T2  - Life
T2  - Life
T1  - Genetic Aspects of Micronutrients Important for Inflammatory Bowel Disease
IS  - 10
SP  - 1623
VL  - 12
DO  - 10.3390/life12101623
ER  - 
@article{
author = "Dragasevic, Sanja and Stanković, Biljana and Kotur, Nikola and Milutinovic, Aleksandra Sokic and Milovanovic, Tamara and Stojkovic Lalosevic, Milica and Stojanovic, Maja and Pavlović, Sonja and Popovic, Dragan",
year = "2022",
abstract = "Inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) are complex diseases whose etiology is associated with genetic and environmental risk factors, among which are diet and gut microbiota. To date, IBD is an incurable disease and the main goal of its treatment is to reduce symptoms, prevent complications, and improve nutritional status and the quality of life. Patients with IBD usually suffer from nutritional deficiency with imbalances of specific micronutrient levels that contribute to the further deterioration of the disease. Therefore, along with medications usually used for IBD treatment, therapeutic strategies also include the supplementation of micronutrients such as vitamin D, folic acid, iron, and zinc. Micronutrient supplementation tailored according to individual needs could help patients to maintain overall health, avoid the triggering of symptoms, and support remission. The identification of individuals’ genotypes associated with the absorption, transport and metabolism of micronutrients can modify future clinical practice in IBD and enable individualized treatment. This review discusses the personalized approach with respect to genetics related to micronutrients commonly used in inflammatory bowel disease treatment.",
journal = "Life, Life",
title = "Genetic Aspects of Micronutrients Important for Inflammatory Bowel Disease",
number = "10",
pages = "1623",
volume = "12",
doi = "10.3390/life12101623"
}
Dragasevic, S., Stanković, B., Kotur, N., Milutinovic, A. S., Milovanovic, T., Stojkovic Lalosevic, M., Stojanovic, M., Pavlović, S.,& Popovic, D.. (2022). Genetic Aspects of Micronutrients Important for Inflammatory Bowel Disease. in Life, 12(10), 1623.
https://doi.org/10.3390/life12101623
Dragasevic S, Stanković B, Kotur N, Milutinovic AS, Milovanovic T, Stojkovic Lalosevic M, Stojanovic M, Pavlović S, Popovic D. Genetic Aspects of Micronutrients Important for Inflammatory Bowel Disease. in Life. 2022;12(10):1623.
doi:10.3390/life12101623 .
Dragasevic, Sanja, Stanković, Biljana, Kotur, Nikola, Milutinovic, Aleksandra Sokic, Milovanovic, Tamara, Stojkovic Lalosevic, Milica, Stojanovic, Maja, Pavlović, Sonja, Popovic, Dragan, "Genetic Aspects of Micronutrients Important for Inflammatory Bowel Disease" in Life, 12, no. 10 (2022):1623,
https://doi.org/10.3390/life12101623 . .
2
4
5

Farmakogenomika vinkristinom indukovane periferne neuropatije kod dece sa akutnom limfoblastnom leukemijom u Srbiji - iskustvo jednog centra

Ristivojević, Bojan; Kotur, Nikola; Stanković, Biljana; Gašić, Vladimir; Lazić, Jelena; Pavlović, Sonja; Zukić, Branka

(Srpsko lekarsko društvo, Beograd, 2022)

TY  - JOUR
AU  - Ristivojević, Bojan
AU  - Kotur, Nikola
AU  - Stanković, Biljana
AU  - Gašić, Vladimir
AU  - Lazić, Jelena
AU  - Pavlović, Sonja
AU  - Zukić, Branka
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1569
AB  - Uvod/Cilj Vinkristin je jedan od ključnih lekova u protokolima lečenja dečje akutne limfoblastne leukemije (ALL). Vinkristin dovodi do destabilizacije mikrotubula, čime se ćelija zaustavlja u metafazi i indukuje apoptoza. Takođe dovodi do degradacije aksona i poremećaja aksonskog transporta, uzrokujući vinkristinom indukovanu perifernu neuropatiju (VIPN). Cilj ove studije bio je da istraži povezanost pet varijanti u farmakogenima uključenim u metabolizam vinkristina kod dece obolele od ALL koja su razvila VIPN, u Srbiji. Takođe, cilj nam je bio da otkrijemo kandidate za nove farmakogenomske markere VIPN-a u srpskoj populaciji. Metode Detekcija varijanti gena CYP3A5, CEP72, ACTG1, MIR3117 i MIR4481 izvedena je metodologijom zasnovanom na PCR-u i sekvenciranju. Statističkim metodama je ispitana njihova asocijacija sa VIPN-om kod 56 pedijatrijskih bolesnika obolelih od ALL. Urađena je i populaciona vinkristin farmakogenomska analiza 17 farmakogena iz postojećih podataka dobijenih sekvenciranjem nove generacije u srpskoj populaciji. Podaci o distribuciji frekvencija alela za evropsko stanovništvo preuzeti su iz javnih baza podataka. Rezultati Tokom lečenja, 17,86% bolesnika je razvilo VIPN. Asocijativne analize pokazale su da nijedna genetička varijanta nije bila povezana sa VIPN-om u našoj studiji. Naše populaciono farmakogenomsko istraživanje nije otkrilo validne farmakovarijante za VIPN. Naši rezultati ne preporučuju preventivno farmakogenetičko ispitivanje vinkristina u Srbiji. Zaključak Potreban je sveobuhvatniji pristup kako bi se identifikovao panel gena kojim bi se mogao objasniti razvoj VIPN-a posle primene vinkristina kod pedijatrijskih bolesnika obolelih od ALL. Bolje osmišljene studije asocijacija na nivou genoma (GWAS) i robusniji alati koji koriste veštačku inteligenciju doveli bi do dizajniranja panela farmakogena za preventivno testiranje predispozicije za razvoj VIPN-a, doprinoseći individualizaciji i unapređenju terapije dece obolele od ALL.
AB  - Introduction/Objective Vincristine (VCR) is one of the key drugs in current treatment protocols for pediatric acute lymphoblastic leukemia (ALL). By destabilizing microtubules, VCR arrests cells in metaphase, inducing apoptosis of malignant cells. VCR also causes axonal degradation and impairment of axonal transport, which leads to VCR-induced peripheral neuropathy (VIPN). This study aimed to investigate the association of five variants in pharmacogenes involved in VCR metabolism with VIPN in Serbian ALL children. We also wanted to discover candidate pharmacogenomic markers of VIPN in Serbian population. Methods PCR and sequencing-based methodology was used to detect variants in CYP3A5, CEP72, ACTG1, MIR3117, and MIR4481 genes. Statistical analyses were performed for investigating their association with VIPN in 56 pediatric ALL patients. Population VCR pharmacogenomics analysis of 17 pharmacogenes from in-house next-generation sequencing data was also done. Data on allele frequency distribution for the European population were extracted from public databases. Results During the treatment, 17.86% of patients developed VIPN. Association analyses have shown that none of the genetic variants contributed to the occurrence of VIPN in our study. Population pharmacogenomics study did not reveal valid candidate pharmacovariants for VIPN. Our results suggested that pre-emptive pharmacogenetic testing for VCR is not applicable presently. Conclusion More comprehensive approaches are needed to identify the panel of genes that could explain the VIPN development after VCR administration in ALL patients. Utilizing better designed genome-wide association studies and more robust artificial intelligence-based tools would provide a panel of pharmacogenes for pre-emptive tests of VIPN to individualize therapy for ALL in children.
PB  - Srpsko lekarsko društvo, Beograd
T2  - Srpski arhiv za celokupno lekarstvo
T1  - Farmakogenomika vinkristinom indukovane periferne neuropatije kod dece sa akutnom limfoblastnom leukemijom u Srbiji - iskustvo jednog centra
T1  - The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia: A single center experience
EP  - 58
IS  - 1-2
SP  - 53
VL  - 150
DO  - 10.2298/SARH210813099R
ER  - 
@article{
author = "Ristivojević, Bojan and Kotur, Nikola and Stanković, Biljana and Gašić, Vladimir and Lazić, Jelena and Pavlović, Sonja and Zukić, Branka",
year = "2022",
abstract = "Uvod/Cilj Vinkristin je jedan od ključnih lekova u protokolima lečenja dečje akutne limfoblastne leukemije (ALL). Vinkristin dovodi do destabilizacije mikrotubula, čime se ćelija zaustavlja u metafazi i indukuje apoptoza. Takođe dovodi do degradacije aksona i poremećaja aksonskog transporta, uzrokujući vinkristinom indukovanu perifernu neuropatiju (VIPN). Cilj ove studije bio je da istraži povezanost pet varijanti u farmakogenima uključenim u metabolizam vinkristina kod dece obolele od ALL koja su razvila VIPN, u Srbiji. Takođe, cilj nam je bio da otkrijemo kandidate za nove farmakogenomske markere VIPN-a u srpskoj populaciji. Metode Detekcija varijanti gena CYP3A5, CEP72, ACTG1, MIR3117 i MIR4481 izvedena je metodologijom zasnovanom na PCR-u i sekvenciranju. Statističkim metodama je ispitana njihova asocijacija sa VIPN-om kod 56 pedijatrijskih bolesnika obolelih od ALL. Urađena je i populaciona vinkristin farmakogenomska analiza 17 farmakogena iz postojećih podataka dobijenih sekvenciranjem nove generacije u srpskoj populaciji. Podaci o distribuciji frekvencija alela za evropsko stanovništvo preuzeti su iz javnih baza podataka. Rezultati Tokom lečenja, 17,86% bolesnika je razvilo VIPN. Asocijativne analize pokazale su da nijedna genetička varijanta nije bila povezana sa VIPN-om u našoj studiji. Naše populaciono farmakogenomsko istraživanje nije otkrilo validne farmakovarijante za VIPN. Naši rezultati ne preporučuju preventivno farmakogenetičko ispitivanje vinkristina u Srbiji. Zaključak Potreban je sveobuhvatniji pristup kako bi se identifikovao panel gena kojim bi se mogao objasniti razvoj VIPN-a posle primene vinkristina kod pedijatrijskih bolesnika obolelih od ALL. Bolje osmišljene studije asocijacija na nivou genoma (GWAS) i robusniji alati koji koriste veštačku inteligenciju doveli bi do dizajniranja panela farmakogena za preventivno testiranje predispozicije za razvoj VIPN-a, doprinoseći individualizaciji i unapređenju terapije dece obolele od ALL., Introduction/Objective Vincristine (VCR) is one of the key drugs in current treatment protocols for pediatric acute lymphoblastic leukemia (ALL). By destabilizing microtubules, VCR arrests cells in metaphase, inducing apoptosis of malignant cells. VCR also causes axonal degradation and impairment of axonal transport, which leads to VCR-induced peripheral neuropathy (VIPN). This study aimed to investigate the association of five variants in pharmacogenes involved in VCR metabolism with VIPN in Serbian ALL children. We also wanted to discover candidate pharmacogenomic markers of VIPN in Serbian population. Methods PCR and sequencing-based methodology was used to detect variants in CYP3A5, CEP72, ACTG1, MIR3117, and MIR4481 genes. Statistical analyses were performed for investigating their association with VIPN in 56 pediatric ALL patients. Population VCR pharmacogenomics analysis of 17 pharmacogenes from in-house next-generation sequencing data was also done. Data on allele frequency distribution for the European population were extracted from public databases. Results During the treatment, 17.86% of patients developed VIPN. Association analyses have shown that none of the genetic variants contributed to the occurrence of VIPN in our study. Population pharmacogenomics study did not reveal valid candidate pharmacovariants for VIPN. Our results suggested that pre-emptive pharmacogenetic testing for VCR is not applicable presently. Conclusion More comprehensive approaches are needed to identify the panel of genes that could explain the VIPN development after VCR administration in ALL patients. Utilizing better designed genome-wide association studies and more robust artificial intelligence-based tools would provide a panel of pharmacogenes for pre-emptive tests of VIPN to individualize therapy for ALL in children.",
publisher = "Srpsko lekarsko društvo, Beograd",
journal = "Srpski arhiv za celokupno lekarstvo",
title = "Farmakogenomika vinkristinom indukovane periferne neuropatije kod dece sa akutnom limfoblastnom leukemijom u Srbiji - iskustvo jednog centra, The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia: A single center experience",
pages = "58-53",
number = "1-2",
volume = "150",
doi = "10.2298/SARH210813099R"
}
Ristivojević, B., Kotur, N., Stanković, B., Gašić, V., Lazić, J., Pavlović, S.,& Zukić, B.. (2022). Farmakogenomika vinkristinom indukovane periferne neuropatije kod dece sa akutnom limfoblastnom leukemijom u Srbiji - iskustvo jednog centra. in Srpski arhiv za celokupno lekarstvo
Srpsko lekarsko društvo, Beograd., 150(1-2), 53-58.
https://doi.org/10.2298/SARH210813099R
Ristivojević B, Kotur N, Stanković B, Gašić V, Lazić J, Pavlović S, Zukić B. Farmakogenomika vinkristinom indukovane periferne neuropatije kod dece sa akutnom limfoblastnom leukemijom u Srbiji - iskustvo jednog centra. in Srpski arhiv za celokupno lekarstvo. 2022;150(1-2):53-58.
doi:10.2298/SARH210813099R .
Ristivojević, Bojan, Kotur, Nikola, Stanković, Biljana, Gašić, Vladimir, Lazić, Jelena, Pavlović, Sonja, Zukić, Branka, "Farmakogenomika vinkristinom indukovane periferne neuropatije kod dece sa akutnom limfoblastnom leukemijom u Srbiji - iskustvo jednog centra" in Srpski arhiv za celokupno lekarstvo, 150, no. 1-2 (2022):53-58,
https://doi.org/10.2298/SARH210813099R . .

Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population

Zecević, Marko; Kotur, Nikola; Ristivojević, Bojan; Gašić, Vladimir; Skodrić-Trifunović, Vesna; Stjepanović, Mihailo; Stevanović, Goran; Lavadinović, Lidija; Zukić, Branka; Pavlović, Sonja; Stanković, Biljana

(Frontiers Media Sa, Lausanne, 2022)

TY  - JOUR
AU  - Zecević, Marko
AU  - Kotur, Nikola
AU  - Ristivojević, Bojan
AU  - Gašić, Vladimir
AU  - Skodrić-Trifunović, Vesna
AU  - Stjepanović, Mihailo
AU  - Stevanović, Goran
AU  - Lavadinović, Lidija
AU  - Zukić, Branka
AU  - Pavlović, Sonja
AU  - Stanković, Biljana
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1515
AB  - Host genetics, an important contributor to the COVID-19 clinical susceptibility and severity, currently is the focus of multiple genome-wide association studies (GWAS) in populations affected by the pandemic. This is the first study from Serbia that performed a GWAS of COVID-19 outcomes to identify genetic risk markers of disease severity. A group of 128 hospitalized COVID-19 patients from the Serbian population was enrolled in the study. We conducted a GWAS comparing (1) patients with pneumonia (n = 80) against patients without pneumonia (n = 48), and (2) severe (n = 34) against mild disease (n = 48) patients, using a genotyping array followed by imputation of missing genotypes. We have detected a significant signal associated with COVID-19 related pneumonia at locus 13q21.33, with a peak residing upstream of the gene KLHL1 (p = 1.91 x 10(-8)). Our study also replicated a previously reported COVID-19 risk locus at 3p21.31, identifying lead variants in SACM1L and LZTFL1 genes suggestively associated with pneumonia (p = 7.54 x 10(-6)) and severe COVID-19 (p = 6.88 x 10(-7)), respectively. Suggestive association with COVID-19 pneumonia has also been observed at chromosomes 5p15.33 (IRX, NDUFS6, MRPL36, p = 2.81 x 10(-6)), 5q11.2 (ESM1, p = 6.59 x 10(-6)), and 9p23 (TYRP1, LURAP1L, p = 8.69 x 10(-6)). The genes located in or near the risk loci are expressed in neural or lung tissues, and have been previously associated with respiratory diseases such as asthma and COVID-19 or reported as differentially expressed in COVID-19 gene expression profiling studies. Our results revealed novel risk loci for pneumonia and severe COVID-19 disease which could contribute to a better understanding of the COVID-19 host genetics in different populations.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Genetics
T1  - Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population
VL  - 13
DO  - 10.3389/fgene.2022.911010
ER  - 
@article{
author = "Zecević, Marko and Kotur, Nikola and Ristivojević, Bojan and Gašić, Vladimir and Skodrić-Trifunović, Vesna and Stjepanović, Mihailo and Stevanović, Goran and Lavadinović, Lidija and Zukić, Branka and Pavlović, Sonja and Stanković, Biljana",
year = "2022",
abstract = "Host genetics, an important contributor to the COVID-19 clinical susceptibility and severity, currently is the focus of multiple genome-wide association studies (GWAS) in populations affected by the pandemic. This is the first study from Serbia that performed a GWAS of COVID-19 outcomes to identify genetic risk markers of disease severity. A group of 128 hospitalized COVID-19 patients from the Serbian population was enrolled in the study. We conducted a GWAS comparing (1) patients with pneumonia (n = 80) against patients without pneumonia (n = 48), and (2) severe (n = 34) against mild disease (n = 48) patients, using a genotyping array followed by imputation of missing genotypes. We have detected a significant signal associated with COVID-19 related pneumonia at locus 13q21.33, with a peak residing upstream of the gene KLHL1 (p = 1.91 x 10(-8)). Our study also replicated a previously reported COVID-19 risk locus at 3p21.31, identifying lead variants in SACM1L and LZTFL1 genes suggestively associated with pneumonia (p = 7.54 x 10(-6)) and severe COVID-19 (p = 6.88 x 10(-7)), respectively. Suggestive association with COVID-19 pneumonia has also been observed at chromosomes 5p15.33 (IRX, NDUFS6, MRPL36, p = 2.81 x 10(-6)), 5q11.2 (ESM1, p = 6.59 x 10(-6)), and 9p23 (TYRP1, LURAP1L, p = 8.69 x 10(-6)). The genes located in or near the risk loci are expressed in neural or lung tissues, and have been previously associated with respiratory diseases such as asthma and COVID-19 or reported as differentially expressed in COVID-19 gene expression profiling studies. Our results revealed novel risk loci for pneumonia and severe COVID-19 disease which could contribute to a better understanding of the COVID-19 host genetics in different populations.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Genetics",
title = "Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population",
volume = "13",
doi = "10.3389/fgene.2022.911010"
}
Zecević, M., Kotur, N., Ristivojević, B., Gašić, V., Skodrić-Trifunović, V., Stjepanović, M., Stevanović, G., Lavadinović, L., Zukić, B., Pavlović, S.,& Stanković, B.. (2022). Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population. in Frontiers in Genetics
Frontiers Media Sa, Lausanne., 13.
https://doi.org/10.3389/fgene.2022.911010
Zecević M, Kotur N, Ristivojević B, Gašić V, Skodrić-Trifunović V, Stjepanović M, Stevanović G, Lavadinović L, Zukić B, Pavlović S, Stanković B. Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population. in Frontiers in Genetics. 2022;13.
doi:10.3389/fgene.2022.911010 .
Zecević, Marko, Kotur, Nikola, Ristivojević, Bojan, Gašić, Vladimir, Skodrić-Trifunović, Vesna, Stjepanović, Mihailo, Stevanović, Goran, Lavadinović, Lidija, Zukić, Branka, Pavlović, Sonja, Stanković, Biljana, "Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population" in Frontiers in Genetics, 13 (2022),
https://doi.org/10.3389/fgene.2022.911010 . .
1
10
8

Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection

Klaassen, Kristel; Stanković, Biljana; Zukić, Branka; Kotur, Nikola; Gašić, Vladimir; Pavlović, Sonja; Stojiljković, Maja

(Springernature, London, 2022)

TY  - CONF
AU  - Klaassen, Kristel
AU  - Stanković, Biljana
AU  - Zukić, Branka
AU  - Kotur, Nikola
AU  - Gašić, Vladimir
AU  - Pavlović, Sonja
AU  - Stojiljković, Maja
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1577
PB  - Springernature, London
C3  - European Journal of Human Genetics
T1  - Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection
EP  - 603
IS  - SUPPL 1
SP  - 603
VL  - 30
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1577
ER  - 
@conference{
author = "Klaassen, Kristel and Stanković, Biljana and Zukić, Branka and Kotur, Nikola and Gašić, Vladimir and Pavlović, Sonja and Stojiljković, Maja",
year = "2022",
publisher = "Springernature, London",
journal = "European Journal of Human Genetics",
title = "Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection",
pages = "603-603",
number = "SUPPL 1",
volume = "30",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1577"
}
Klaassen, K., Stanković, B., Zukić, B., Kotur, N., Gašić, V., Pavlović, S.,& Stojiljković, M.. (2022). Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection. in European Journal of Human Genetics
Springernature, London., 30(SUPPL 1), 603-603.
https://hdl.handle.net/21.15107/rcub_imagine_1577
Klaassen K, Stanković B, Zukić B, Kotur N, Gašić V, Pavlović S, Stojiljković M. Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection. in European Journal of Human Genetics. 2022;30(SUPPL 1):603-603.
https://hdl.handle.net/21.15107/rcub_imagine_1577 .
Klaassen, Kristel, Stanković, Biljana, Zukić, Branka, Kotur, Nikola, Gašić, Vladimir, Pavlović, Sonja, Stojiljković, Maja, "Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection" in European Journal of Human Genetics, 30, no. SUPPL 1 (2022):603-603,
https://hdl.handle.net/21.15107/rcub_imagine_1577 .

Pharmacogenomics and pharmacotranscriptomics of glucocorticoids in pediatric acute lymphoblastic leukemia

Gašić, Vladimir; Pavlović, Đorđe; Stanković, Biljana; Kotur, Nikola; Zukić, Branka; Pavlović, Sonja

(IntechOpen, 2021)

TY  - CHAP
AU  - Gašić, Vladimir
AU  - Pavlović, Đorđe
AU  - Stanković, Biljana
AU  - Kotur, Nikola
AU  - Zukić, Branka
AU  - Pavlović, Sonja
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1620
AB  - Pharmacogenomics and pharmacotranscriptomics contribute to more efficient and safer treatment of many diseases, especially malignancies. Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy during childhood. Glucocorticoids, prednisone and dexamethasone, represent the basis of chemotherapy in pediatric ALL. Therapy causes side effects in 75% of patients and 1–3% of pediatric ALL patients die because of therapy side effects rather than the disease itself. Due to this fact, pharmacogenomics and pharmacotranscriptomics have gained key positions in this field. There is a growing knowledge of pharmacogenomics and pharmacotranscriptomics markers relevant for the success of the glucocorticoid treatment of children with ALL. New technologies, such as next-generation sequencing (NGS) have created a possibility for designing panels of pharmacogenomics and pharmacotranscriptomics markers related to the response to glucocorticoid drugs. Optimization of these panels through population pharmacogenomic studies leads to new knowledge that could open the doors widely to pre-emptive pharmacogenomic testing.
PB  - IntechOpen
T2  - Corticosteroids : A Paradigmatic Drug Class
T2  - glucocorticoids
T2  - pediatric acute lymphoblastic leukemia
T2  - pharmacogenomics
T2  - pharmacotranscriptomics
T2  - population pharmacogenomics
T1  - Pharmacogenomics and pharmacotranscriptomics of glucocorticoids in pediatric acute lymphoblastic leukemia
EP  - 17
SP  - 1
DO  - 10.5772/intechopen.98887
ER  - 
@inbook{
author = "Gašić, Vladimir and Pavlović, Đorđe and Stanković, Biljana and Kotur, Nikola and Zukić, Branka and Pavlović, Sonja",
year = "2021",
abstract = "Pharmacogenomics and pharmacotranscriptomics contribute to more efficient and safer treatment of many diseases, especially malignancies. Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy during childhood. Glucocorticoids, prednisone and dexamethasone, represent the basis of chemotherapy in pediatric ALL. Therapy causes side effects in 75% of patients and 1–3% of pediatric ALL patients die because of therapy side effects rather than the disease itself. Due to this fact, pharmacogenomics and pharmacotranscriptomics have gained key positions in this field. There is a growing knowledge of pharmacogenomics and pharmacotranscriptomics markers relevant for the success of the glucocorticoid treatment of children with ALL. New technologies, such as next-generation sequencing (NGS) have created a possibility for designing panels of pharmacogenomics and pharmacotranscriptomics markers related to the response to glucocorticoid drugs. Optimization of these panels through population pharmacogenomic studies leads to new knowledge that could open the doors widely to pre-emptive pharmacogenomic testing.",
publisher = "IntechOpen",
journal = "Corticosteroids : A Paradigmatic Drug Class, glucocorticoids, pediatric acute lymphoblastic leukemia, pharmacogenomics, pharmacotranscriptomics, population pharmacogenomics",
booktitle = "Pharmacogenomics and pharmacotranscriptomics of glucocorticoids in pediatric acute lymphoblastic leukemia",
pages = "17-1",
doi = "10.5772/intechopen.98887"
}
Gašić, V., Pavlović, Đ., Stanković, B., Kotur, N., Zukić, B.,& Pavlović, S.. (2021). Pharmacogenomics and pharmacotranscriptomics of glucocorticoids in pediatric acute lymphoblastic leukemia. in Corticosteroids : A Paradigmatic Drug Class
IntechOpen., 1-17.
https://doi.org/10.5772/intechopen.98887
Gašić V, Pavlović Đ, Stanković B, Kotur N, Zukić B, Pavlović S. Pharmacogenomics and pharmacotranscriptomics of glucocorticoids in pediatric acute lymphoblastic leukemia. in Corticosteroids : A Paradigmatic Drug Class. 2021;:1-17.
doi:10.5772/intechopen.98887 .
Gašić, Vladimir, Pavlović, Đorđe, Stanković, Biljana, Kotur, Nikola, Zukić, Branka, Pavlović, Sonja, "Pharmacogenomics and pharmacotranscriptomics of glucocorticoids in pediatric acute lymphoblastic leukemia" in Corticosteroids : A Paradigmatic Drug Class (2021):1-17,
https://doi.org/10.5772/intechopen.98887 . .

Precision medicine and COVID-19: importance of host genome profiling and bioinformatics

Zukić, Branka; Kotur, Nikola; Stanković, Biljana

(Novi Sad : Faculty of Sciences, Department of Biology and Ecology, 2021)

TY  - CONF
AU  - Zukić, Branka
AU  - Kotur, Nikola
AU  - Stanković, Biljana
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1878
AB  - Clinical picture and course of the disease in patients with COVID-19 vary from asymptomatic to lethal.
Precision medicine could discover the cause of this phenomenon by analyzing the individual genomic
profiles of the patients.
We aimed to understand a host genetic component of COVID-19 focusing on variants in genes encoding
proteases and genes involved in innate immunity, important for susceptibility and resistance to SARS-CoV-2
infection. Also, we wanted to identify phamracogenes and pharmacogenomics markers associated with
drugs used for COVID-19 treatment in different clinical protocols in Serbia, and to compare the results
with various world populations.
Genotype information of 143 individuals of Serbian origin was extracted from database previously obtained
using TruSight One Gene Panel (Illumina). Variants in genes encoding proteases and genes involved in innate
immunity were identified and analysed in silico (PolyPhen-2, SIFT, MutPred2, Swiss-Pdb Viewer) to predict
the impact of the variants to the structure and/or function of proteins. Genotype data from Serbian population
was compared with European and 4 super-populations (total 2504 subjects). Data were extracted from
VCF files of Phase 3 variant calls of the 1000 Genomes Project (1kGP) sample collection via Ensembl Data
Slicer Tool. The level of population genetic variability at each selected loci was examined using the maximal
global differences in minor allele frequencies (delta MAF) calculated by subtracting the maximum and the
minimum MAF across analyzed population groups, and Fst statistics. Fisher exact test was used to measure
differences in genotypes distributions between Serbian and 1kGP populations, applying Bonferoni correction.
R software was utilized for genotype data manipulation and statistical calculations.
Based on high alternative allele frequencies in population and the functional effect of the variants, we identified
variants in genes encoding proteases and involved in the innate immunity that might be relevant for the
host response to SARS-CoV-2 infection. The potential pharmacogenomics markers in pharmacogenes relevant
for COVID-19 treatment were also identified. Bioinformatics tools integrated into precision medicine
could contribute to better understanding of inter-individual and population-specific genetic susceptibility and
resistance to the SARS-CoV-2 infection, therapy response inconsistencies, and could be applied to improve
the outcome of the COVID-19 patients.
PB  - Novi Sad : Faculty of Sciences, Department of Biology and Ecology
C3  - Biologia Serbica
T1  - Precision medicine and COVID-19: importance of host genome profiling and bioinformatics
IS  - 1 (Special Edition)
SP  - 31
VL  - 43
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1878
ER  - 
@conference{
author = "Zukić, Branka and Kotur, Nikola and Stanković, Biljana",
year = "2021",
abstract = "Clinical picture and course of the disease in patients with COVID-19 vary from asymptomatic to lethal.
Precision medicine could discover the cause of this phenomenon by analyzing the individual genomic
profiles of the patients.
We aimed to understand a host genetic component of COVID-19 focusing on variants in genes encoding
proteases and genes involved in innate immunity, important for susceptibility and resistance to SARS-CoV-2
infection. Also, we wanted to identify phamracogenes and pharmacogenomics markers associated with
drugs used for COVID-19 treatment in different clinical protocols in Serbia, and to compare the results
with various world populations.
Genotype information of 143 individuals of Serbian origin was extracted from database previously obtained
using TruSight One Gene Panel (Illumina). Variants in genes encoding proteases and genes involved in innate
immunity were identified and analysed in silico (PolyPhen-2, SIFT, MutPred2, Swiss-Pdb Viewer) to predict
the impact of the variants to the structure and/or function of proteins. Genotype data from Serbian population
was compared with European and 4 super-populations (total 2504 subjects). Data were extracted from
VCF files of Phase 3 variant calls of the 1000 Genomes Project (1kGP) sample collection via Ensembl Data
Slicer Tool. The level of population genetic variability at each selected loci was examined using the maximal
global differences in minor allele frequencies (delta MAF) calculated by subtracting the maximum and the
minimum MAF across analyzed population groups, and Fst statistics. Fisher exact test was used to measure
differences in genotypes distributions between Serbian and 1kGP populations, applying Bonferoni correction.
R software was utilized for genotype data manipulation and statistical calculations.
Based on high alternative allele frequencies in population and the functional effect of the variants, we identified
variants in genes encoding proteases and involved in the innate immunity that might be relevant for the
host response to SARS-CoV-2 infection. The potential pharmacogenomics markers in pharmacogenes relevant
for COVID-19 treatment were also identified. Bioinformatics tools integrated into precision medicine
could contribute to better understanding of inter-individual and population-specific genetic susceptibility and
resistance to the SARS-CoV-2 infection, therapy response inconsistencies, and could be applied to improve
the outcome of the COVID-19 patients.",
publisher = "Novi Sad : Faculty of Sciences, Department of Biology and Ecology",
journal = "Biologia Serbica",
title = "Precision medicine and COVID-19: importance of host genome profiling and bioinformatics",
number = "1 (Special Edition)",
pages = "31",
volume = "43",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1878"
}
Zukić, B., Kotur, N.,& Stanković, B.. (2021). Precision medicine and COVID-19: importance of host genome profiling and bioinformatics. in Biologia Serbica
Novi Sad : Faculty of Sciences, Department of Biology and Ecology., 43(1 (Special Edition)), 31.
https://hdl.handle.net/21.15107/rcub_imagine_1878
Zukić B, Kotur N, Stanković B. Precision medicine and COVID-19: importance of host genome profiling and bioinformatics. in Biologia Serbica. 2021;43(1 (Special Edition)):31.
https://hdl.handle.net/21.15107/rcub_imagine_1878 .
Zukić, Branka, Kotur, Nikola, Stanković, Biljana, "Precision medicine and COVID-19: importance of host genome profiling and bioinformatics" in Biologia Serbica, 43, no. 1 (Special Edition) (2021):31,
https://hdl.handle.net/21.15107/rcub_imagine_1878 .

Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity

Kotur, Nikola; Skakić, Anita; Klaassen, Kristel; Gašić, Vladimir; Zukić, Branka; Skodrić-Trifunović, Vesna; Stjepanović, Mihailo; Zivković, Zorica; Ostojić, Olivera; Stevanović, Goran; Lavadinović, Lidija; Pavlović, Sonja; Stanković, Biljana

(Frontiers Media Sa, Lausanne, 2021)

TY  - JOUR
AU  - Kotur, Nikola
AU  - Skakić, Anita
AU  - Klaassen, Kristel
AU  - Gašić, Vladimir
AU  - Zukić, Branka
AU  - Skodrić-Trifunović, Vesna
AU  - Stjepanović, Mihailo
AU  - Zivković, Zorica
AU  - Ostojić, Olivera
AU  - Stevanović, Goran
AU  - Lavadinović, Lidija
AU  - Pavlović, Sonja
AU  - Stanković, Biljana
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1439
AB  - Background: COVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The emerging amount of data indicates that vitamin D, zinc and selenium could be important for clinical presentation of COVID-19. Here, we investigated association of genetic variants related to the altered level and bioavailability of vitamin D, zinc and selenium with clinical severity of COVID-19. Methods: We analyzed variants in genes significant for the status of vitamin D (DHCR7/NADSYN1 rs12785878, GC rs2282679, CYP2R1 rs10741657, and VDR rs2228570), zinc (PPCDC rs2120019) and selenium (DMGDH rs17823744) in 120 Serbian adult and pediatric COVID-19 patients using allelic discrimination. Furthermore, we carried out comparative population genetic analysis among European and other worldwide populations to investigate variation in allelic frequencies of selected variants. Results: Study showed that DHCR7/NADSYN rs12785878 and CYP2R1 rs10741657 variants were associated with severe COVID-19 in adults (p = 0.03, p = 0.017, respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the odds for developing severe disease, OR 0.21 (0.05-0.9) and OR 5.9 (1.4-25.2), respectively. There were no associations between selected genetic variants and disease severity in pediatric patients. Comparative population genetic analysis revealed that Serbian population had the lowest frequency of CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and 0.66 in Spanish and Italian population, respectively), suggesting that other populations should also investigate the relationship of CYP2R1 variant and the COVID-19 disease course. Conclusion: The results of the study indicated that vitamin D related genetic variants were implicated in severe COVID-19 in adults. This could direct prevention strategies based on population specific nutrigenetic profiles.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Nutrition
T1  - Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity
VL  - 8
DO  - 10.3389/fnut.2021.689419
ER  - 
@article{
author = "Kotur, Nikola and Skakić, Anita and Klaassen, Kristel and Gašić, Vladimir and Zukić, Branka and Skodrić-Trifunović, Vesna and Stjepanović, Mihailo and Zivković, Zorica and Ostojić, Olivera and Stevanović, Goran and Lavadinović, Lidija and Pavlović, Sonja and Stanković, Biljana",
year = "2021",
abstract = "Background: COVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The emerging amount of data indicates that vitamin D, zinc and selenium could be important for clinical presentation of COVID-19. Here, we investigated association of genetic variants related to the altered level and bioavailability of vitamin D, zinc and selenium with clinical severity of COVID-19. Methods: We analyzed variants in genes significant for the status of vitamin D (DHCR7/NADSYN1 rs12785878, GC rs2282679, CYP2R1 rs10741657, and VDR rs2228570), zinc (PPCDC rs2120019) and selenium (DMGDH rs17823744) in 120 Serbian adult and pediatric COVID-19 patients using allelic discrimination. Furthermore, we carried out comparative population genetic analysis among European and other worldwide populations to investigate variation in allelic frequencies of selected variants. Results: Study showed that DHCR7/NADSYN rs12785878 and CYP2R1 rs10741657 variants were associated with severe COVID-19 in adults (p = 0.03, p = 0.017, respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the odds for developing severe disease, OR 0.21 (0.05-0.9) and OR 5.9 (1.4-25.2), respectively. There were no associations between selected genetic variants and disease severity in pediatric patients. Comparative population genetic analysis revealed that Serbian population had the lowest frequency of CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and 0.66 in Spanish and Italian population, respectively), suggesting that other populations should also investigate the relationship of CYP2R1 variant and the COVID-19 disease course. Conclusion: The results of the study indicated that vitamin D related genetic variants were implicated in severe COVID-19 in adults. This could direct prevention strategies based on population specific nutrigenetic profiles.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Nutrition",
title = "Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity",
volume = "8",
doi = "10.3389/fnut.2021.689419"
}
Kotur, N., Skakić, A., Klaassen, K., Gašić, V., Zukić, B., Skodrić-Trifunović, V., Stjepanović, M., Zivković, Z., Ostojić, O., Stevanović, G., Lavadinović, L., Pavlović, S.,& Stanković, B.. (2021). Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity. in Frontiers in Nutrition
Frontiers Media Sa, Lausanne., 8.
https://doi.org/10.3389/fnut.2021.689419
Kotur N, Skakić A, Klaassen K, Gašić V, Zukić B, Skodrić-Trifunović V, Stjepanović M, Zivković Z, Ostojić O, Stevanović G, Lavadinović L, Pavlović S, Stanković B. Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity. in Frontiers in Nutrition. 2021;8.
doi:10.3389/fnut.2021.689419 .
Kotur, Nikola, Skakić, Anita, Klaassen, Kristel, Gašić, Vladimir, Zukić, Branka, Skodrić-Trifunović, Vesna, Stjepanović, Mihailo, Zivković, Zorica, Ostojić, Olivera, Stevanović, Goran, Lavadinović, Lidija, Pavlović, Sonja, Stanković, Biljana, "Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity" in Frontiers in Nutrition, 8 (2021),
https://doi.org/10.3389/fnut.2021.689419 . .
52
24
23

Personalizovana medicina i COVID-19: značaj genomskog profilisanja pacijenata i bioinformatike

Zukić, Branka; Stanković, Biljana; Kotur, Nikola

(Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo, 2021)

TY  - CHAP
AU  - Zukić, Branka
AU  - Stanković, Biljana
AU  - Kotur, Nikola
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1653
AB  - Novi koronavirus SARS-CoV-2, uzročnik upale pluća, sposoban je da zarazi ljude i izazove novu bolest COVID- 19 koja je preopteretila zdravstvene sisteme širom planete i izazvala globalnu ekonomsku krizu. Klinička slika i tok bolesti kod pacijenata obolelih od COVID-19 varira od asimptomatske do letalnog ishoda. Kako se radi o istom uzročniku bolesti, individualni genomski profil pacijenta krije odgovor na pitanje medicinske nauke o uzroku ovog fenomena. U radu su sumirana dosadašnja znanja o genetičkim markerima koji su odgovorni za široki spektar kliničkih slika, kao i da li se već može primeniti individualizovan pristup lečenju. Prikazane su dosada istraživane varijante u genima (sa osvrtom na populacione specifičnosti) odgovorne za predispoziciju i odgovor na SARS-CoV-2 virusnu infekciju, farmakogenetičke varijante od značaja za lekove koji se koriste u lečenju pacijenata obolelih od COVID-19, kao i nutrigenetički markeri u genima važnim za metabolizam mikronutrijenata, vitamina D, selena i cinka, koji se takođe koriste u terapiji pacijenata sa COVID-19. Udruženi napor istraživača, multidisciplinarni pristup, dostupnost modernih tehnologija koje imaju kapacitet analize celokupnih genoma, buduće sveobuhvatnije studije sa dobro okarakterisanim grupama pacijenata, kao i razvoj robusnijih bioinformatičkih alata koji koriste mašinsko učenje i napredne statističke metode, omogućiće identifikaciju novih genetičkih markera čoveka povezanih sa COVID-19, bolje razumevanje same patofiziologije bolesti, razvoj prave ciljane terapije kao i istaći značaj nutrigenomike i farmakogenomike za primenu personalizovane medicine u lečenju COVID-19.
AB  - The new cause of pneumonia, coronavirus SARS-CoV-2, capable of infecting people and causing the new disease
COVID-19, overloaded health systems around the planet and caused a global economic crisis. The clinical
presentation and the course of the disease in COVID-19 patients vary from asymptomatic to lethal. As it
is the same cause of the disease, the individual genomic profile of the patient reveals the answer to the
question of medical science about the cause of this phenomenon. The paper summarizes the current knowledge
about genetic markers responsible for a wide range of clinical pictures, as well as whether an individualized
approach to treatment can already be applied. The variants identified so far in genes (with reference
to population specifics) responsible for predisposition and response to SARS-CoV-2 viral infection, pharmacogenetic
variants of importance for drugs used in the treatment of patients with COVID-19, as well as nutrigenetic
markers in genes important for the metabolism of the micronutrients, vitamin D, selenium and
zinc, also used in the therapy of patients with COVID-19, are presented. The combined effort of researchers,
a multidisciplinary approach, the availability of modern technologies that have the capacity to analyze entire
genomes, future more comprehensive studies with well-characterized patient groups, and the development
of more robust bioinformatics tools using machine learning and advanced statistical methods will
enable the identification of novel human genetic markers associated with COVID -19, better understanding
of the pathophysiology of the disease, development of the proper targeted therapy as well as point out the
importance of nutrigenomics and pharmacogenomics for the application of personalized medicine in the
treatment of COVID-19.
PB  - Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo
T2  - Trendovi u molekularnoj Biologiji
T1  - Personalizovana medicina i COVID-19: značaj genomskog profilisanja pacijenata i bioinformatike
T1  - Personalized medicine and COVID-19: the importance of genomic host profiling and bioinformatics
EP  - 20
IS  - 1
SP  - 6
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1653
ER  - 
@inbook{
author = "Zukić, Branka and Stanković, Biljana and Kotur, Nikola",
year = "2021",
abstract = "Novi koronavirus SARS-CoV-2, uzročnik upale pluća, sposoban je da zarazi ljude i izazove novu bolest COVID- 19 koja je preopteretila zdravstvene sisteme širom planete i izazvala globalnu ekonomsku krizu. Klinička slika i tok bolesti kod pacijenata obolelih od COVID-19 varira od asimptomatske do letalnog ishoda. Kako se radi o istom uzročniku bolesti, individualni genomski profil pacijenta krije odgovor na pitanje medicinske nauke o uzroku ovog fenomena. U radu su sumirana dosadašnja znanja o genetičkim markerima koji su odgovorni za široki spektar kliničkih slika, kao i da li se već može primeniti individualizovan pristup lečenju. Prikazane su dosada istraživane varijante u genima (sa osvrtom na populacione specifičnosti) odgovorne za predispoziciju i odgovor na SARS-CoV-2 virusnu infekciju, farmakogenetičke varijante od značaja za lekove koji se koriste u lečenju pacijenata obolelih od COVID-19, kao i nutrigenetički markeri u genima važnim za metabolizam mikronutrijenata, vitamina D, selena i cinka, koji se takođe koriste u terapiji pacijenata sa COVID-19. Udruženi napor istraživača, multidisciplinarni pristup, dostupnost modernih tehnologija koje imaju kapacitet analize celokupnih genoma, buduće sveobuhvatnije studije sa dobro okarakterisanim grupama pacijenata, kao i razvoj robusnijih bioinformatičkih alata koji koriste mašinsko učenje i napredne statističke metode, omogućiće identifikaciju novih genetičkih markera čoveka povezanih sa COVID-19, bolje razumevanje same patofiziologije bolesti, razvoj prave ciljane terapije kao i istaći značaj nutrigenomike i farmakogenomike za primenu personalizovane medicine u lečenju COVID-19., The new cause of pneumonia, coronavirus SARS-CoV-2, capable of infecting people and causing the new disease
COVID-19, overloaded health systems around the planet and caused a global economic crisis. The clinical
presentation and the course of the disease in COVID-19 patients vary from asymptomatic to lethal. As it
is the same cause of the disease, the individual genomic profile of the patient reveals the answer to the
question of medical science about the cause of this phenomenon. The paper summarizes the current knowledge
about genetic markers responsible for a wide range of clinical pictures, as well as whether an individualized
approach to treatment can already be applied. The variants identified so far in genes (with reference
to population specifics) responsible for predisposition and response to SARS-CoV-2 viral infection, pharmacogenetic
variants of importance for drugs used in the treatment of patients with COVID-19, as well as nutrigenetic
markers in genes important for the metabolism of the micronutrients, vitamin D, selenium and
zinc, also used in the therapy of patients with COVID-19, are presented. The combined effort of researchers,
a multidisciplinary approach, the availability of modern technologies that have the capacity to analyze entire
genomes, future more comprehensive studies with well-characterized patient groups, and the development
of more robust bioinformatics tools using machine learning and advanced statistical methods will
enable the identification of novel human genetic markers associated with COVID -19, better understanding
of the pathophysiology of the disease, development of the proper targeted therapy as well as point out the
importance of nutrigenomics and pharmacogenomics for the application of personalized medicine in the
treatment of COVID-19.",
publisher = "Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo",
journal = "Trendovi u molekularnoj Biologiji",
booktitle = "Personalizovana medicina i COVID-19: značaj genomskog profilisanja pacijenata i bioinformatike, Personalized medicine and COVID-19: the importance of genomic host profiling and bioinformatics",
pages = "20-6",
number = "1",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1653"
}
Zukić, B., Stanković, B.,& Kotur, N.. (2021). Personalizovana medicina i COVID-19: značaj genomskog profilisanja pacijenata i bioinformatike. in Trendovi u molekularnoj Biologiji
Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo.(1), 6-20.
https://hdl.handle.net/21.15107/rcub_imagine_1653
Zukić B, Stanković B, Kotur N. Personalizovana medicina i COVID-19: značaj genomskog profilisanja pacijenata i bioinformatike. in Trendovi u molekularnoj Biologiji. 2021;(1):6-20.
https://hdl.handle.net/21.15107/rcub_imagine_1653 .
Zukić, Branka, Stanković, Biljana, Kotur, Nikola, "Personalizovana medicina i COVID-19: značaj genomskog profilisanja pacijenata i bioinformatike" in Trendovi u molekularnoj Biologiji, no. 1 (2021):6-20,
https://hdl.handle.net/21.15107/rcub_imagine_1653 .

Machine Learning Modeling from Omics Data as Prospective Tool for Improvement of Inflammatory Bowel Disease Diagnosis and Clinical Classifications

Stanković, Biljana; Kotur, Nikola; Nikčević, Gordana; Gašić, Vladimir; Zukić, Branka; Pavlović, Sonja

(MDPI, Basel, 2021)

TY  - JOUR
AU  - Stanković, Biljana
AU  - Kotur, Nikola
AU  - Nikčević, Gordana
AU  - Gašić, Vladimir
AU  - Zukić, Branka
AU  - Pavlović, Sonja
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1460
AB  - Research of inflammatory bowel disease (IBD) has identified numerous molecular players involved in the disease development. Even so, the understanding of IBD is incomplete, while disease treatment is still far from the precision medicine. Reliable diagnostic and prognostic biomarkers in IBD are limited which may reduce efficient therapeutic outcomes. High-throughput technologies and artificial intelligence emerged as powerful tools in search of unrevealed molecular patterns that could give important insights into IBD pathogenesis and help to address unmet clinical needs. Machine learning, a subtype of artificial intelligence, uses complex mathematical algorithms to learn from existing data in order to predict future outcomes. The scientific community has been increasingly employing machine learning for the prediction of IBD outcomes from comprehensive patient data-clinical records, genomic, transcriptomic, proteomic, metagenomic, and other IBD relevant omics data. This review aims to present fundamental principles behind machine learning modeling and its current application in IBD research with the focus on studies that explored genomic and transcriptomic data. We described different strategies used for dealing with omics data and outlined the best-performing methods. Before being translated into clinical settings, the developed machine learning models should be tested in independent prospective studies as well as randomized controlled trials.
PB  - MDPI, Basel
T2  - Genes
T1  - Machine Learning Modeling from Omics Data as Prospective Tool for Improvement of Inflammatory Bowel Disease Diagnosis and Clinical Classifications
IS  - 9
VL  - 12
DO  - 10.3390/genes12091438
ER  - 
@article{
author = "Stanković, Biljana and Kotur, Nikola and Nikčević, Gordana and Gašić, Vladimir and Zukić, Branka and Pavlović, Sonja",
year = "2021",
abstract = "Research of inflammatory bowel disease (IBD) has identified numerous molecular players involved in the disease development. Even so, the understanding of IBD is incomplete, while disease treatment is still far from the precision medicine. Reliable diagnostic and prognostic biomarkers in IBD are limited which may reduce efficient therapeutic outcomes. High-throughput technologies and artificial intelligence emerged as powerful tools in search of unrevealed molecular patterns that could give important insights into IBD pathogenesis and help to address unmet clinical needs. Machine learning, a subtype of artificial intelligence, uses complex mathematical algorithms to learn from existing data in order to predict future outcomes. The scientific community has been increasingly employing machine learning for the prediction of IBD outcomes from comprehensive patient data-clinical records, genomic, transcriptomic, proteomic, metagenomic, and other IBD relevant omics data. This review aims to present fundamental principles behind machine learning modeling and its current application in IBD research with the focus on studies that explored genomic and transcriptomic data. We described different strategies used for dealing with omics data and outlined the best-performing methods. Before being translated into clinical settings, the developed machine learning models should be tested in independent prospective studies as well as randomized controlled trials.",
publisher = "MDPI, Basel",
journal = "Genes",
title = "Machine Learning Modeling from Omics Data as Prospective Tool for Improvement of Inflammatory Bowel Disease Diagnosis and Clinical Classifications",
number = "9",
volume = "12",
doi = "10.3390/genes12091438"
}
Stanković, B., Kotur, N., Nikčević, G., Gašić, V., Zukić, B.,& Pavlović, S.. (2021). Machine Learning Modeling from Omics Data as Prospective Tool for Improvement of Inflammatory Bowel Disease Diagnosis and Clinical Classifications. in Genes
MDPI, Basel., 12(9).
https://doi.org/10.3390/genes12091438
Stanković B, Kotur N, Nikčević G, Gašić V, Zukić B, Pavlović S. Machine Learning Modeling from Omics Data as Prospective Tool for Improvement of Inflammatory Bowel Disease Diagnosis and Clinical Classifications. in Genes. 2021;12(9).
doi:10.3390/genes12091438 .
Stanković, Biljana, Kotur, Nikola, Nikčević, Gordana, Gašić, Vladimir, Zukić, Branka, Pavlović, Sonja, "Machine Learning Modeling from Omics Data as Prospective Tool for Improvement of Inflammatory Bowel Disease Diagnosis and Clinical Classifications" in Genes, 12, no. 9 (2021),
https://doi.org/10.3390/genes12091438 . .
1
9
7

The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls

Mihaljević, Marina; Franić, Dusanka; Soldatović, Ivan; Lukić, Iva; Andrić-Petrović, Sanja; Mirjanić, Tijana; Stanković, Biljana; Zukić, Branka; Zeljić, Katarina; Gašić, Vladimir; Novaković, Ivana; Pavlović, Sonja; Adžić, Miroslav; Marić, Nadja P.

(Pergamon-Elsevier Science Ltd, Oxford, 2021)

TY  - JOUR
AU  - Mihaljević, Marina
AU  - Franić, Dusanka
AU  - Soldatović, Ivan
AU  - Lukić, Iva
AU  - Andrić-Petrović, Sanja
AU  - Mirjanić, Tijana
AU  - Stanković, Biljana
AU  - Zukić, Branka
AU  - Zeljić, Katarina
AU  - Gašić, Vladimir
AU  - Novaković, Ivana
AU  - Pavlović, Sonja
AU  - Adžić, Miroslav
AU  - Marić, Nadja P.
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1451
AB  - Hypothalamic-pituitary-adrenal (HPA) axis activity mediates the relationship between childhood trauma (CT) and psychosis. The FKBP5 gene, one of the key regulators of HPA axis activity after stress exposure, has been found associated with psychosis. Allele-specific and CT related FKBP5 demethylation in intron 7 was revealed in different psychiatric disorders. However, no studies have investigated FKBP5 methylation in subjects with different genetic liability for psychosis. A total of 144 participants were included in the study: 48 patients with psychotic disorders, 50 unaffected siblings, and 46 healthy controls. CT was assessed by Childhood Trauma Questionnaire. The FKBP5 rs1360780 was genotyped and FKBP5 methylation analyses were performed using bisulfite conversion followed by Sanger sequencing at three CpG sites in intron 7. Mixed linear model was used to assess group differences depending on rs1360780 T allele and CT. Results showed a significant T allele-dependent decrease of FKBP5 methylation in patients compared to unaffected siblings and controls. Effect of interaction between T allele and CT exposure on FKBP5 demethylation was found in controls. No effect of both risk factors (T allele and CT) on FKBP5 methylation level was found in unaffected siblings. We confirmed previous evidence of the association between the FKBP5 rs1360780 T allele, CT, and decreased FKBP5 methylation in intron 7. Allele-specific FKBP5 demethylation found in patients could shed a light on altered HPA axis activity in a subgroup of patients related to stress-induced psychosis. FKBP5 methylation and potential protective mechanisms in unaffected siblings after trauma exposure require further investigation.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Psychoneuroendocrinology
T1  - The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls
VL  - 128
DO  - 10.1016/j.psyneuen.2021.105205
ER  - 
@article{
author = "Mihaljević, Marina and Franić, Dusanka and Soldatović, Ivan and Lukić, Iva and Andrić-Petrović, Sanja and Mirjanić, Tijana and Stanković, Biljana and Zukić, Branka and Zeljić, Katarina and Gašić, Vladimir and Novaković, Ivana and Pavlović, Sonja and Adžić, Miroslav and Marić, Nadja P.",
year = "2021",
abstract = "Hypothalamic-pituitary-adrenal (HPA) axis activity mediates the relationship between childhood trauma (CT) and psychosis. The FKBP5 gene, one of the key regulators of HPA axis activity after stress exposure, has been found associated with psychosis. Allele-specific and CT related FKBP5 demethylation in intron 7 was revealed in different psychiatric disorders. However, no studies have investigated FKBP5 methylation in subjects with different genetic liability for psychosis. A total of 144 participants were included in the study: 48 patients with psychotic disorders, 50 unaffected siblings, and 46 healthy controls. CT was assessed by Childhood Trauma Questionnaire. The FKBP5 rs1360780 was genotyped and FKBP5 methylation analyses were performed using bisulfite conversion followed by Sanger sequencing at three CpG sites in intron 7. Mixed linear model was used to assess group differences depending on rs1360780 T allele and CT. Results showed a significant T allele-dependent decrease of FKBP5 methylation in patients compared to unaffected siblings and controls. Effect of interaction between T allele and CT exposure on FKBP5 demethylation was found in controls. No effect of both risk factors (T allele and CT) on FKBP5 methylation level was found in unaffected siblings. We confirmed previous evidence of the association between the FKBP5 rs1360780 T allele, CT, and decreased FKBP5 methylation in intron 7. Allele-specific FKBP5 demethylation found in patients could shed a light on altered HPA axis activity in a subgroup of patients related to stress-induced psychosis. FKBP5 methylation and potential protective mechanisms in unaffected siblings after trauma exposure require further investigation.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Psychoneuroendocrinology",
title = "The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls",
volume = "128",
doi = "10.1016/j.psyneuen.2021.105205"
}
Mihaljević, M., Franić, D., Soldatović, I., Lukić, I., Andrić-Petrović, S., Mirjanić, T., Stanković, B., Zukić, B., Zeljić, K., Gašić, V., Novaković, I., Pavlović, S., Adžić, M.,& Marić, N. P.. (2021). The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls. in Psychoneuroendocrinology
Pergamon-Elsevier Science Ltd, Oxford., 128.
https://doi.org/10.1016/j.psyneuen.2021.105205
Mihaljević M, Franić D, Soldatović I, Lukić I, Andrić-Petrović S, Mirjanić T, Stanković B, Zukić B, Zeljić K, Gašić V, Novaković I, Pavlović S, Adžić M, Marić NP. The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls. in Psychoneuroendocrinology. 2021;128.
doi:10.1016/j.psyneuen.2021.105205 .
Mihaljević, Marina, Franić, Dusanka, Soldatović, Ivan, Lukić, Iva, Andrić-Petrović, Sanja, Mirjanić, Tijana, Stanković, Biljana, Zukić, Branka, Zeljić, Katarina, Gašić, Vladimir, Novaković, Ivana, Pavlović, Sonja, Adžić, Miroslav, Marić, Nadja P., "The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls" in Psychoneuroendocrinology, 128 (2021),
https://doi.org/10.1016/j.psyneuen.2021.105205 . .
2
7
2
6

Cytotoxicity of the gold complex based on mercaptotriazole - A comparison with the conventional cyanide electrolyte

Dimitrijević, Silvana B.; Alagić, Sladana; Pavlović, Sonja; Stanković, Biljana; Kotur, Nikola; Ivanović, Aleksandra; Dimitrijević, Stevan P.

(Elsevier, Amsterdam, 2021)

TY  - JOUR
AU  - Dimitrijević, Silvana B.
AU  - Alagić, Sladana
AU  - Pavlović, Sonja
AU  - Stanković, Biljana
AU  - Kotur, Nikola
AU  - Ivanović, Aleksandra
AU  - Dimitrijević, Stevan P.
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1480
AB  - The study presents the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay results on human erythroleukemia K562 cell line to compare the toxicity of electrolytes based on the mercaptotriazole gold complex (Au-MT) and gold potassium cyanide. Solutions immediately after mixing and after three months at different concentrations were compared, with a prolonged aging period, to a year, for the electrolytes at pH = 9. Lower toxicity of new organic gold complex at pH = 4, 7, and 12 than of alkaline cyanide electrolyte, but higher at pH = 2, was determined. The solution of the Au-MT at pH = 9 had comparable, but lower cell toxicity in the whole investigated period.
PB  - Elsevier, Amsterdam
T2  - Journal of the Indian Chemical Society
T1  - Cytotoxicity of the gold complex based on mercaptotriazole - A comparison with the conventional cyanide electrolyte
IS  - 11
VL  - 98
DO  - 10.1016/j.jics.2021.100219
ER  - 
@article{
author = "Dimitrijević, Silvana B. and Alagić, Sladana and Pavlović, Sonja and Stanković, Biljana and Kotur, Nikola and Ivanović, Aleksandra and Dimitrijević, Stevan P.",
year = "2021",
abstract = "The study presents the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay results on human erythroleukemia K562 cell line to compare the toxicity of electrolytes based on the mercaptotriazole gold complex (Au-MT) and gold potassium cyanide. Solutions immediately after mixing and after three months at different concentrations were compared, with a prolonged aging period, to a year, for the electrolytes at pH = 9. Lower toxicity of new organic gold complex at pH = 4, 7, and 12 than of alkaline cyanide electrolyte, but higher at pH = 2, was determined. The solution of the Au-MT at pH = 9 had comparable, but lower cell toxicity in the whole investigated period.",
publisher = "Elsevier, Amsterdam",
journal = "Journal of the Indian Chemical Society",
title = "Cytotoxicity of the gold complex based on mercaptotriazole - A comparison with the conventional cyanide electrolyte",
number = "11",
volume = "98",
doi = "10.1016/j.jics.2021.100219"
}
Dimitrijević, S. B., Alagić, S., Pavlović, S., Stanković, B., Kotur, N., Ivanović, A.,& Dimitrijević, S. P.. (2021). Cytotoxicity of the gold complex based on mercaptotriazole - A comparison with the conventional cyanide electrolyte. in Journal of the Indian Chemical Society
Elsevier, Amsterdam., 98(11).
https://doi.org/10.1016/j.jics.2021.100219
Dimitrijević SB, Alagić S, Pavlović S, Stanković B, Kotur N, Ivanović A, Dimitrijević SP. Cytotoxicity of the gold complex based on mercaptotriazole - A comparison with the conventional cyanide electrolyte. in Journal of the Indian Chemical Society. 2021;98(11).
doi:10.1016/j.jics.2021.100219 .
Dimitrijević, Silvana B., Alagić, Sladana, Pavlović, Sonja, Stanković, Biljana, Kotur, Nikola, Ivanović, Aleksandra, Dimitrijević, Stevan P., "Cytotoxicity of the gold complex based on mercaptotriazole - A comparison with the conventional cyanide electrolyte" in Journal of the Indian Chemical Society, 98, no. 11 (2021),
https://doi.org/10.1016/j.jics.2021.100219 . .
1
1

Pharmacogenomic Markers of Methotrexate Response in the Consolidation Phase of Pediatric Acute Lymphoblastic Leukemia Treatment

Kotur, Nikola; Lazić, Jelena; Ristivojević, Bojan; Stanković, Biljana; Gašić, Vladimir; Dokmanović, Lidija; Krstovski, Nada; Milosević, Goran; Janić, Dragana; Zukić, Branka; Pavlović, Sonja

(MDPI, Basel, 2020)

TY  - JOUR
AU  - Kotur, Nikola
AU  - Lazić, Jelena
AU  - Ristivojević, Bojan
AU  - Stanković, Biljana
AU  - Gašić, Vladimir
AU  - Dokmanović, Lidija
AU  - Krstovski, Nada
AU  - Milosević, Goran
AU  - Janić, Dragana
AU  - Zukić, Branka
AU  - Pavlović, Sonja
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1322
AB  - Methotrexate (MTX) is one of the staples of pediatric acute lymphoblastic leukemia (ALL) treatment. MTX targets the folate metabolic pathway (FMP). Abnormal function of the enzymes in FMP, due to genetic aberrations, leads to adverse drug reactions. The aim of this study was to investigate variants in pharmacogenes involved in FMP and their association with MTX pharmacokinetics (MTX elimination profile) and toxicity in the consolidation therapy phase of pediatric ALL patients. Eleven variants in the thymidylate synthetase (TYMS), methylenetetrahydrofolate reductase (MTHFR), dihydrofolate reductase (DHFR), SLC19A1 and SLCO1B genes were analyzed in 148 patients, using PCR- and sequencing-based methodology. For the Serbian and European control groups, data on allele frequency distribution were extracted from in-house and public databases. Our results show that the A allele of SLC19A1 c.80 variant contributes to slow MTX elimination. Additionally, the AA genotype of the same variant is a predictor of MTX-related hepatotoxicity. Patients homozygous for TYMS 6bp deletion were more likely to experience gastrointestinal toxicity. No allele frequency dissimilarity was found for the analyzed variants between Serbian and European populations. Statistical modelling did not show a joint effect of analyzed variants. Our results indicate that SLC19A1 c.80 variant and TYMS 6bp deletion are the most promising pharmacogenomic markers of MTX response in pediatric ALL patients.
PB  - MDPI, Basel
T2  - Genes
T1  - Pharmacogenomic Markers of Methotrexate Response in the Consolidation Phase of Pediatric Acute Lymphoblastic Leukemia Treatment
IS  - 4
VL  - 11
DO  - 10.3390/genes11040468
ER  - 
@article{
author = "Kotur, Nikola and Lazić, Jelena and Ristivojević, Bojan and Stanković, Biljana and Gašić, Vladimir and Dokmanović, Lidija and Krstovski, Nada and Milosević, Goran and Janić, Dragana and Zukić, Branka and Pavlović, Sonja",
year = "2020",
abstract = "Methotrexate (MTX) is one of the staples of pediatric acute lymphoblastic leukemia (ALL) treatment. MTX targets the folate metabolic pathway (FMP). Abnormal function of the enzymes in FMP, due to genetic aberrations, leads to adverse drug reactions. The aim of this study was to investigate variants in pharmacogenes involved in FMP and their association with MTX pharmacokinetics (MTX elimination profile) and toxicity in the consolidation therapy phase of pediatric ALL patients. Eleven variants in the thymidylate synthetase (TYMS), methylenetetrahydrofolate reductase (MTHFR), dihydrofolate reductase (DHFR), SLC19A1 and SLCO1B genes were analyzed in 148 patients, using PCR- and sequencing-based methodology. For the Serbian and European control groups, data on allele frequency distribution were extracted from in-house and public databases. Our results show that the A allele of SLC19A1 c.80 variant contributes to slow MTX elimination. Additionally, the AA genotype of the same variant is a predictor of MTX-related hepatotoxicity. Patients homozygous for TYMS 6bp deletion were more likely to experience gastrointestinal toxicity. No allele frequency dissimilarity was found for the analyzed variants between Serbian and European populations. Statistical modelling did not show a joint effect of analyzed variants. Our results indicate that SLC19A1 c.80 variant and TYMS 6bp deletion are the most promising pharmacogenomic markers of MTX response in pediatric ALL patients.",
publisher = "MDPI, Basel",
journal = "Genes",
title = "Pharmacogenomic Markers of Methotrexate Response in the Consolidation Phase of Pediatric Acute Lymphoblastic Leukemia Treatment",
number = "4",
volume = "11",
doi = "10.3390/genes11040468"
}
Kotur, N., Lazić, J., Ristivojević, B., Stanković, B., Gašić, V., Dokmanović, L., Krstovski, N., Milosević, G., Janić, D., Zukić, B.,& Pavlović, S.. (2020). Pharmacogenomic Markers of Methotrexate Response in the Consolidation Phase of Pediatric Acute Lymphoblastic Leukemia Treatment. in Genes
MDPI, Basel., 11(4).
https://doi.org/10.3390/genes11040468
Kotur N, Lazić J, Ristivojević B, Stanković B, Gašić V, Dokmanović L, Krstovski N, Milosević G, Janić D, Zukić B, Pavlović S. Pharmacogenomic Markers of Methotrexate Response in the Consolidation Phase of Pediatric Acute Lymphoblastic Leukemia Treatment. in Genes. 2020;11(4).
doi:10.3390/genes11040468 .
Kotur, Nikola, Lazić, Jelena, Ristivojević, Bojan, Stanković, Biljana, Gašić, Vladimir, Dokmanović, Lidija, Krstovski, Nada, Milosević, Goran, Janić, Dragana, Zukić, Branka, Pavlović, Sonja, "Pharmacogenomic Markers of Methotrexate Response in the Consolidation Phase of Pediatric Acute Lymphoblastic Leukemia Treatment" in Genes, 11, no. 4 (2020),
https://doi.org/10.3390/genes11040468 . .
17
18

Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection

Klaassen, Kristel; Stanković, Biljana; Zukić, Branka; Kotur, Nikola; Gašić, Vladimir; Pavlović, Sonja; Stojiljković, Maja

(Elsevier, Amsterdam, 2020)

TY  - JOUR
AU  - Klaassen, Kristel
AU  - Stanković, Biljana
AU  - Zukić, Branka
AU  - Kotur, Nikola
AU  - Gašić, Vladimir
AU  - Pavlović, Sonja
AU  - Stojiljković, Maja
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1350
AB  - New coronavirus SARS-CoV-2 is capable to infect humans and cause a novel disease COVID-19. Aiming to understand a host genetic component of COVID-19, we focused on variants in genes encoding proteases and genes involved in innate immunity that could be important for susceptibility and resistance to SARS-CoV-2 infection. Analysis of sequence data of coding regions of FURIN, PLG, PRSS1, TMPRSS11a, MBL2 and OAS1 genes in 143 unrelated individuals from Serbian population identified 22 variants with potential functional effect. In silico analyses (PolyPhen-2, SIFT, MutPred2 and Swiss-Pdb Viewer) predicted that 10 variants could impact the structure and/or function of proteins. These protein-altering variants (p.Gly146Ser in FURIN; p.Arg261His and p.Ala494Val in PLG; p.Asn54Lys in PRSS1; p.Arg52Cys, p.Gly54Asp and p.Gly57Glu in MBL2; p.Arg47Gln, p.Ile99Val and p.Arg130His in OAS1) may have predictive value for inter-individual differences in the response to the SARS-CoV-2 infection. Next, we performed comparative population analysis for the same variants using extracted data from the 1000 Genomes project. Population genetic variability was assessed using delta MAF and Fst statistics. Our study pointed to 7 variants in PLG, TMPRSS11a, MBL2 and OAS1 genes with noticeable divergence in allelic frequencies between populations worldwide. Three of them, all in MBL2 gene, were predicted to be damaging, making them the most promising population-specific markers related to SARS-CoV-2 infection. Comparing allelic frequencies between Serbian and other populations, we found that the highest level of genetic divergence related to selected loci was observed with African, followed by East Asian, Central and South American and South Asian populations. When compared with European populations, the highest divergence was observed with Italian population. In conclusion, we identified 4 variants in genes encoding proteases (FURIN, PLG and PRSS1) and 6 in genes involved in the innate immunity (MBL2 and OAS1) that might be relevant for the host response to SARS-CoV-2 infection.
PB  - Elsevier, Amsterdam
T2  - Infection Genetics and Evolution
T1  - Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection
VL  - 84
DO  - 10.1016/j.meegid.2020.104498
ER  - 
@article{
author = "Klaassen, Kristel and Stanković, Biljana and Zukić, Branka and Kotur, Nikola and Gašić, Vladimir and Pavlović, Sonja and Stojiljković, Maja",
year = "2020",
abstract = "New coronavirus SARS-CoV-2 is capable to infect humans and cause a novel disease COVID-19. Aiming to understand a host genetic component of COVID-19, we focused on variants in genes encoding proteases and genes involved in innate immunity that could be important for susceptibility and resistance to SARS-CoV-2 infection. Analysis of sequence data of coding regions of FURIN, PLG, PRSS1, TMPRSS11a, MBL2 and OAS1 genes in 143 unrelated individuals from Serbian population identified 22 variants with potential functional effect. In silico analyses (PolyPhen-2, SIFT, MutPred2 and Swiss-Pdb Viewer) predicted that 10 variants could impact the structure and/or function of proteins. These protein-altering variants (p.Gly146Ser in FURIN; p.Arg261His and p.Ala494Val in PLG; p.Asn54Lys in PRSS1; p.Arg52Cys, p.Gly54Asp and p.Gly57Glu in MBL2; p.Arg47Gln, p.Ile99Val and p.Arg130His in OAS1) may have predictive value for inter-individual differences in the response to the SARS-CoV-2 infection. Next, we performed comparative population analysis for the same variants using extracted data from the 1000 Genomes project. Population genetic variability was assessed using delta MAF and Fst statistics. Our study pointed to 7 variants in PLG, TMPRSS11a, MBL2 and OAS1 genes with noticeable divergence in allelic frequencies between populations worldwide. Three of them, all in MBL2 gene, were predicted to be damaging, making them the most promising population-specific markers related to SARS-CoV-2 infection. Comparing allelic frequencies between Serbian and other populations, we found that the highest level of genetic divergence related to selected loci was observed with African, followed by East Asian, Central and South American and South Asian populations. When compared with European populations, the highest divergence was observed with Italian population. In conclusion, we identified 4 variants in genes encoding proteases (FURIN, PLG and PRSS1) and 6 in genes involved in the innate immunity (MBL2 and OAS1) that might be relevant for the host response to SARS-CoV-2 infection.",
publisher = "Elsevier, Amsterdam",
journal = "Infection Genetics and Evolution",
title = "Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection",
volume = "84",
doi = "10.1016/j.meegid.2020.104498"
}
Klaassen, K., Stanković, B., Zukić, B., Kotur, N., Gašić, V., Pavlović, S.,& Stojiljković, M.. (2020). Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection. in Infection Genetics and Evolution
Elsevier, Amsterdam., 84.
https://doi.org/10.1016/j.meegid.2020.104498
Klaassen K, Stanković B, Zukić B, Kotur N, Gašić V, Pavlović S, Stojiljković M. Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection. in Infection Genetics and Evolution. 2020;84.
doi:10.1016/j.meegid.2020.104498 .
Klaassen, Kristel, Stanković, Biljana, Zukić, Branka, Kotur, Nikola, Gašić, Vladimir, Pavlović, Sonja, Stojiljković, Maja, "Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection" in Infection Genetics and Evolution, 84 (2020),
https://doi.org/10.1016/j.meegid.2020.104498 . .
6
20
14

Farmakogenomski profil odgovora na terapiju za COVID-19 u populaciji Srbije i poređenje sa populacijama širom sveta

Stanković, Biljana; Kotur, Nikola; Gašić, Vladimir; Klaassen, Kristel; Ristivojević, Bojan; Stojiljković, Maja; Pavlović, Sonja; Zukić, Branka

(Društvo medicinskih biohemičara Srbije, Beograd i Versita, 2020)

TY  - JOUR
AU  - Stanković, Biljana
AU  - Kotur, Nikola
AU  - Gašić, Vladimir
AU  - Klaassen, Kristel
AU  - Ristivojević, Bojan
AU  - Stojiljković, Maja
AU  - Pavlović, Sonja
AU  - Zukić, Branka
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1362
AB  - Uvod: Kako ne postoje odobreni terapeutici za lečenje pacijenata sa COVID-19, mogućnost upotrebe postojećih lekova je postala važna. U nedostatku vremena za testiranje farmakogenomskih markera kod pojedinaca, populaciona farmakogenomika bi mogla biti od koristi u predviđanju povećanog rizika za pojavu neželjenih reakcija i neuspeha lečenja kod pacijenata sa COVID-19. Cilj naše studije bio je identifikovanje farmakogena i farmakogenomskih markera povezanih sa lekovima koji se preporučuju za lečenje COVID-19, hlorokin/hidroksihlorokin, azitromicin, lopinavir i ritonavir, u populaciji Srbije i drugim svetskim populacijama. Metode: Podaci o genotipu 143 osobe srpskog porekla dobijeni su iz baze podataka prethodno formirane analizama genoma korišćenjem TruSight One Gene Panel (Illumina). Podaci o genotipu pojedinaca iz različitih svetskih populacija dobijeni su iz Projekta 1000 genoma. Fišerov egzaktni test korišćen je za poređenje učestalosti alela. Rezultati: Identifikovali smo 11 potencijalnih farmakogenomskih markera u 7 farmakogena značajnih za lečenje COVID-19. Na osnovu visoke alterativne učestalosti alela u populaciji Srbije i funkcionalnog efekta varijanti, ABCB1 rs1045642 i rs2032582 mogu biti značajne za smanjeni klirens lekova azitromicina, lopinavira i ritonavira, a varijanta UGT1A7 rs17868323 za hiperbilirubinemiju kod bolesnika sa COVID-19 koji se leče ritonavirom. SLCO1B1 rs4149056 je potencijalni marker odgovora na lopinavir, posebno u populaciji Italije. Naši rezultati potvrdili su da se farmakogenomski profil afričke populacije razlikuje od ostatka sveta. Zaključak: Uzimajući u obzir farmakogenomski profil specifičan za populaciju, preventivno testiranje farmakogena značajnih za lekove koji se koriste u lečenju COVID-19 moglo bi doprineti boljem razumevanju interindividualnih razlika u odgovorima na terapiju i poboljšanju ishoda lečenja pacijenata sa COVID-19.
AB  - Background: Since there are no certified therapeutics to treat COVID-19 patients, drug repurposing became important. With lack of time to test individual pharmacogenomics markers, population pharmacogenomics could be helpful in predicting a higher risk of developing adverse reactions and treatment failure in COVID-19 patients. Aim of our study was to identify pharmacogenes and pharmacogenomics markers associated with drugs recommended for COVID-19 treatment, chloroquine/hydroxychloroquine, azithromycin, lopinavir and ritonavir, in population of Serbia and other world populations. Methods: Genotype information of 143 individuals of Serbian origin was extracted from database previously obtained using TruSight One Gene Panel (Illumina). Genotype data of individuals from different world populations were extracted from the 1000 Genome Project. Fisher's exact test was used for comparison of allele frequencies. Results: We have identified 11 potential pharmacogenomics markers in 7 pharmacogenes relevant for COVID-19 treatment. Based on high alternative allele frequencies in population and the functional effect of the variants, ABCB1 rs1045642 and rs2032582 could be relevant for reduced clearance of azithromycin, lopinavir and ritonavir drugs and UGT1A7 rs17868323 for hyperbilirubinemia in ritonavir treated COVID-19 patients in Serbian population. SLCO1B1 rs4149056 is a potential marker of lopinavir response, especially in Italian population. Our results confirmed that pharmacogenomics profile of African population is different from the rest of the world. Conclusions: Considering population specific pharmacogenomics landscape, preemptive testing for pharmacogenes relevant for drugs used in COVID-19 treatment could contribute to better understanding of the inconsistency in therapy response and could be applied to improve the outcome of the COVID-19 patients.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Farmakogenomski profil odgovora na terapiju za COVID-19 u populaciji Srbije i poređenje sa populacijama širom sveta
T1  - Pharmacogenomics landscape of COVID-19 therapy response in Serbian population and comparison with worldwide populations
EP  - 499
IS  - 4
SP  - 488
VL  - 39
DO  - 10.5937/jomb0-26725
ER  - 
@article{
author = "Stanković, Biljana and Kotur, Nikola and Gašić, Vladimir and Klaassen, Kristel and Ristivojević, Bojan and Stojiljković, Maja and Pavlović, Sonja and Zukić, Branka",
year = "2020",
abstract = "Uvod: Kako ne postoje odobreni terapeutici za lečenje pacijenata sa COVID-19, mogućnost upotrebe postojećih lekova je postala važna. U nedostatku vremena za testiranje farmakogenomskih markera kod pojedinaca, populaciona farmakogenomika bi mogla biti od koristi u predviđanju povećanog rizika za pojavu neželjenih reakcija i neuspeha lečenja kod pacijenata sa COVID-19. Cilj naše studije bio je identifikovanje farmakogena i farmakogenomskih markera povezanih sa lekovima koji se preporučuju za lečenje COVID-19, hlorokin/hidroksihlorokin, azitromicin, lopinavir i ritonavir, u populaciji Srbije i drugim svetskim populacijama. Metode: Podaci o genotipu 143 osobe srpskog porekla dobijeni su iz baze podataka prethodno formirane analizama genoma korišćenjem TruSight One Gene Panel (Illumina). Podaci o genotipu pojedinaca iz različitih svetskih populacija dobijeni su iz Projekta 1000 genoma. Fišerov egzaktni test korišćen je za poređenje učestalosti alela. Rezultati: Identifikovali smo 11 potencijalnih farmakogenomskih markera u 7 farmakogena značajnih za lečenje COVID-19. Na osnovu visoke alterativne učestalosti alela u populaciji Srbije i funkcionalnog efekta varijanti, ABCB1 rs1045642 i rs2032582 mogu biti značajne za smanjeni klirens lekova azitromicina, lopinavira i ritonavira, a varijanta UGT1A7 rs17868323 za hiperbilirubinemiju kod bolesnika sa COVID-19 koji se leče ritonavirom. SLCO1B1 rs4149056 je potencijalni marker odgovora na lopinavir, posebno u populaciji Italije. Naši rezultati potvrdili su da se farmakogenomski profil afričke populacije razlikuje od ostatka sveta. Zaključak: Uzimajući u obzir farmakogenomski profil specifičan za populaciju, preventivno testiranje farmakogena značajnih za lekove koji se koriste u lečenju COVID-19 moglo bi doprineti boljem razumevanju interindividualnih razlika u odgovorima na terapiju i poboljšanju ishoda lečenja pacijenata sa COVID-19., Background: Since there are no certified therapeutics to treat COVID-19 patients, drug repurposing became important. With lack of time to test individual pharmacogenomics markers, population pharmacogenomics could be helpful in predicting a higher risk of developing adverse reactions and treatment failure in COVID-19 patients. Aim of our study was to identify pharmacogenes and pharmacogenomics markers associated with drugs recommended for COVID-19 treatment, chloroquine/hydroxychloroquine, azithromycin, lopinavir and ritonavir, in population of Serbia and other world populations. Methods: Genotype information of 143 individuals of Serbian origin was extracted from database previously obtained using TruSight One Gene Panel (Illumina). Genotype data of individuals from different world populations were extracted from the 1000 Genome Project. Fisher's exact test was used for comparison of allele frequencies. Results: We have identified 11 potential pharmacogenomics markers in 7 pharmacogenes relevant for COVID-19 treatment. Based on high alternative allele frequencies in population and the functional effect of the variants, ABCB1 rs1045642 and rs2032582 could be relevant for reduced clearance of azithromycin, lopinavir and ritonavir drugs and UGT1A7 rs17868323 for hyperbilirubinemia in ritonavir treated COVID-19 patients in Serbian population. SLCO1B1 rs4149056 is a potential marker of lopinavir response, especially in Italian population. Our results confirmed that pharmacogenomics profile of African population is different from the rest of the world. Conclusions: Considering population specific pharmacogenomics landscape, preemptive testing for pharmacogenes relevant for drugs used in COVID-19 treatment could contribute to better understanding of the inconsistency in therapy response and could be applied to improve the outcome of the COVID-19 patients.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Farmakogenomski profil odgovora na terapiju za COVID-19 u populaciji Srbije i poređenje sa populacijama širom sveta, Pharmacogenomics landscape of COVID-19 therapy response in Serbian population and comparison with worldwide populations",
pages = "499-488",
number = "4",
volume = "39",
doi = "10.5937/jomb0-26725"
}
Stanković, B., Kotur, N., Gašić, V., Klaassen, K., Ristivojević, B., Stojiljković, M., Pavlović, S.,& Zukić, B.. (2020). Farmakogenomski profil odgovora na terapiju za COVID-19 u populaciji Srbije i poređenje sa populacijama širom sveta. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 39(4), 488-499.
https://doi.org/10.5937/jomb0-26725
Stanković B, Kotur N, Gašić V, Klaassen K, Ristivojević B, Stojiljković M, Pavlović S, Zukić B. Farmakogenomski profil odgovora na terapiju za COVID-19 u populaciji Srbije i poređenje sa populacijama širom sveta. in Journal of Medical Biochemistry. 2020;39(4):488-499.
doi:10.5937/jomb0-26725 .
Stanković, Biljana, Kotur, Nikola, Gašić, Vladimir, Klaassen, Kristel, Ristivojević, Bojan, Stojiljković, Maja, Pavlović, Sonja, Zukić, Branka, "Farmakogenomski profil odgovora na terapiju za COVID-19 u populaciji Srbije i poređenje sa populacijama širom sveta" in Journal of Medical Biochemistry, 39, no. 4 (2020):488-499,
https://doi.org/10.5937/jomb0-26725 . .
1
7
6

Metabolic Syndrome in Inflammatory Bowel Disease: Association with Genetic Markers of Obesity and Inflammation

Dragasević, Sanja; Stanković, Biljana; Kotur, Nikola; Sokić-Milutinović, Aleksandra; Milovanović, Tamara; Lukić, Snežana; Milosavljević, Tomica; Srzentić Dražilov, Sanja; Klaassen, Kristel; Pavlović, Sonja; Popović, Dragan

(Mary Ann Liebert, Inc, New Rochelle, 2020)

TY  - JOUR
AU  - Dragasević, Sanja
AU  - Stanković, Biljana
AU  - Kotur, Nikola
AU  - Sokić-Milutinović, Aleksandra
AU  - Milovanović, Tamara
AU  - Lukić, Snežana
AU  - Milosavljević, Tomica
AU  - Srzentić Dražilov, Sanja
AU  - Klaassen, Kristel
AU  - Pavlović, Sonja
AU  - Popović, Dragan
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1398
AB  - Background: This study analyzed poorly understood relationship of two overlapping conditions: metabolic syndrome (MeS) and inflammatory bowel disease (IBD), both associated with inflammation in the visceral adipose tissue. Methods: Newly diagnosed 104 IBD patients, of which 50 Crohn's disease (CD) and 54 ulcerative colitis (UC), and 45 non-IBD controls were examined for MeS-related obesity and lipid markers. Th-17 immune genes IL17A, IL17F, IL23A, and TLR9 mRNAs were measured in intestinal mucosa by qRT-PCR. Subjects were genotyped for obesity-associated FTO variant rs9939609 by polymerase chain reaction-amplification refractory mutation system. Results: CD was associated with MeS (P = 0.01), while both CD and UC were associated with central obesity (P = 10(-5), P = 0.002, respectively) and low levels of high-density lipoprotein (HDL) cholesterol (P = 5 x 10(-6), P = 6 x 10(-6), respectively). IBD lipid profile was characterized by decreased total and HDL cholesterol, while low-density lipoprotein cholesterol was reduced only in CD. Negative correlations were found between total cholesterol and CD activity index (P = 0.005), waist circumference and IL17A as well as IL17F mRNA levels in inflamed CD colon (P = 0.003, P = 0.001, respectively). Carriers of FTO rs9939609 AA genotype showed increased risk of CD (OR 2.6, P = 0.01). Conclusions: MeS, central obesity, and dyslipidemia could be important for IBD pathogenesis. This could influence therapeutic approaches and prevention strategies in high-risk groups.
PB  - Mary Ann Liebert, Inc, New Rochelle
T2  - Metabolic Syndrome and Related Disorders
T1  - Metabolic Syndrome in Inflammatory Bowel Disease: Association with Genetic Markers of Obesity and Inflammation
EP  - 38
IS  - 1
SP  - 31
VL  - 18
DO  - 10.1089/met.2019.0090
ER  - 
@article{
author = "Dragasević, Sanja and Stanković, Biljana and Kotur, Nikola and Sokić-Milutinović, Aleksandra and Milovanović, Tamara and Lukić, Snežana and Milosavljević, Tomica and Srzentić Dražilov, Sanja and Klaassen, Kristel and Pavlović, Sonja and Popović, Dragan",
year = "2020",
abstract = "Background: This study analyzed poorly understood relationship of two overlapping conditions: metabolic syndrome (MeS) and inflammatory bowel disease (IBD), both associated with inflammation in the visceral adipose tissue. Methods: Newly diagnosed 104 IBD patients, of which 50 Crohn's disease (CD) and 54 ulcerative colitis (UC), and 45 non-IBD controls were examined for MeS-related obesity and lipid markers. Th-17 immune genes IL17A, IL17F, IL23A, and TLR9 mRNAs were measured in intestinal mucosa by qRT-PCR. Subjects were genotyped for obesity-associated FTO variant rs9939609 by polymerase chain reaction-amplification refractory mutation system. Results: CD was associated with MeS (P = 0.01), while both CD and UC were associated with central obesity (P = 10(-5), P = 0.002, respectively) and low levels of high-density lipoprotein (HDL) cholesterol (P = 5 x 10(-6), P = 6 x 10(-6), respectively). IBD lipid profile was characterized by decreased total and HDL cholesterol, while low-density lipoprotein cholesterol was reduced only in CD. Negative correlations were found between total cholesterol and CD activity index (P = 0.005), waist circumference and IL17A as well as IL17F mRNA levels in inflamed CD colon (P = 0.003, P = 0.001, respectively). Carriers of FTO rs9939609 AA genotype showed increased risk of CD (OR 2.6, P = 0.01). Conclusions: MeS, central obesity, and dyslipidemia could be important for IBD pathogenesis. This could influence therapeutic approaches and prevention strategies in high-risk groups.",
publisher = "Mary Ann Liebert, Inc, New Rochelle",
journal = "Metabolic Syndrome and Related Disorders",
title = "Metabolic Syndrome in Inflammatory Bowel Disease: Association with Genetic Markers of Obesity and Inflammation",
pages = "38-31",
number = "1",
volume = "18",
doi = "10.1089/met.2019.0090"
}
Dragasević, S., Stanković, B., Kotur, N., Sokić-Milutinović, A., Milovanović, T., Lukić, S., Milosavljević, T., Srzentić Dražilov, S., Klaassen, K., Pavlović, S.,& Popović, D.. (2020). Metabolic Syndrome in Inflammatory Bowel Disease: Association with Genetic Markers of Obesity and Inflammation. in Metabolic Syndrome and Related Disorders
Mary Ann Liebert, Inc, New Rochelle., 18(1), 31-38.
https://doi.org/10.1089/met.2019.0090
Dragasević S, Stanković B, Kotur N, Sokić-Milutinović A, Milovanović T, Lukić S, Milosavljević T, Srzentić Dražilov S, Klaassen K, Pavlović S, Popović D. Metabolic Syndrome in Inflammatory Bowel Disease: Association with Genetic Markers of Obesity and Inflammation. in Metabolic Syndrome and Related Disorders. 2020;18(1):31-38.
doi:10.1089/met.2019.0090 .
Dragasević, Sanja, Stanković, Biljana, Kotur, Nikola, Sokić-Milutinović, Aleksandra, Milovanović, Tamara, Lukić, Snežana, Milosavljević, Tomica, Srzentić Dražilov, Sanja, Klaassen, Kristel, Pavlović, Sonja, Popović, Dragan, "Metabolic Syndrome in Inflammatory Bowel Disease: Association with Genetic Markers of Obesity and Inflammation" in Metabolic Syndrome and Related Disorders, 18, no. 1 (2020):31-38,
https://doi.org/10.1089/met.2019.0090 . .
1
26
9
23

Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy

Stanković, Biljana; Dragasević, Sanja; Klaassen, Kristel; Kotur, Nikola; Srzentić Dražilov, Sanja; Zukić, Branka; Sokic Milutinović, Aleksandra; Milovanović, Tamara; Lukić, Snežana; Popović, Dragan; Pavlović, Sonja; Nikčević, Gordana

(Elsevier Gmbh, Munich, 2020)

TY  - JOUR
AU  - Stanković, Biljana
AU  - Dragasević, Sanja
AU  - Klaassen, Kristel
AU  - Kotur, Nikola
AU  - Srzentić Dražilov, Sanja
AU  - Zukić, Branka
AU  - Sokic Milutinović, Aleksandra
AU  - Milovanović, Tamara
AU  - Lukić, Snežana
AU  - Popović, Dragan
AU  - Pavlović, Sonja
AU  - Nikčević, Gordana
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1329
AB  - Background: Crohn's disease (CD) is chronic inflammatory bowel disease with different phenotypic characteristics influencing disease prognosis and therapeutic strategies. The aim of this pilot study was to analyze selected inflammatory and apoptotic markers in non-inflamed and inflamed samples of ileal mucosa of non-stricturing/non-penetrating (NS/NP) and stricturing (S) CD mucosal phenotypes in order to characterize their distinct profiles. Methods: From twenty CD patients (9 NS/NP, 11 S) paired non-inflamed and inflamed ileal biopsies were collected and used for analysis of cytokine (TNF and IL6) and apoptotic (Bcl2, Box, Fas and FasL) genes' expression levels by real-time PCR, while NF kappa B transcriptional potency was assessed by electromobility gel shift assay. Results: Our results demonstrated significant upregulation of TNF and IL6 in inflamed area of both NS/NP (p = 0.03, p = 0.01) and S phenotypes (p = 0.04, p = 0.04), respectively. However, TNF increase was more prominent in NS/NP compared to S inflamed mucosa (p = 0.02). Also, level of proapoptotic Box was significantly higher in NS/NP compared to S inflamed mucosa (p = 0.01). Opposing transcription potency of NF kappa B has been detected between two phenotypes: being decreased in NS/NP (p = 0.07) and increased in S (p = 0.1) inflamed compared to non-inflamed mucosa, demonstrating trend towards statistical significance. Conclusions: We found that two distinct CD phenotypes have specific molecular signatures. Obtained results could direct improvement of current and development of new therapeutic strategies based on more specific molecular stratification of CD patients.
PB  - Elsevier Gmbh, Munich
T2  - Pathology Research and Practice
T1  - Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy
IS  - 6
VL  - 216
DO  - 10.1016/j.prp.2020.152945
ER  - 
@article{
author = "Stanković, Biljana and Dragasević, Sanja and Klaassen, Kristel and Kotur, Nikola and Srzentić Dražilov, Sanja and Zukić, Branka and Sokic Milutinović, Aleksandra and Milovanović, Tamara and Lukić, Snežana and Popović, Dragan and Pavlović, Sonja and Nikčević, Gordana",
year = "2020",
abstract = "Background: Crohn's disease (CD) is chronic inflammatory bowel disease with different phenotypic characteristics influencing disease prognosis and therapeutic strategies. The aim of this pilot study was to analyze selected inflammatory and apoptotic markers in non-inflamed and inflamed samples of ileal mucosa of non-stricturing/non-penetrating (NS/NP) and stricturing (S) CD mucosal phenotypes in order to characterize their distinct profiles. Methods: From twenty CD patients (9 NS/NP, 11 S) paired non-inflamed and inflamed ileal biopsies were collected and used for analysis of cytokine (TNF and IL6) and apoptotic (Bcl2, Box, Fas and FasL) genes' expression levels by real-time PCR, while NF kappa B transcriptional potency was assessed by electromobility gel shift assay. Results: Our results demonstrated significant upregulation of TNF and IL6 in inflamed area of both NS/NP (p = 0.03, p = 0.01) and S phenotypes (p = 0.04, p = 0.04), respectively. However, TNF increase was more prominent in NS/NP compared to S inflamed mucosa (p = 0.02). Also, level of proapoptotic Box was significantly higher in NS/NP compared to S inflamed mucosa (p = 0.01). Opposing transcription potency of NF kappa B has been detected between two phenotypes: being decreased in NS/NP (p = 0.07) and increased in S (p = 0.1) inflamed compared to non-inflamed mucosa, demonstrating trend towards statistical significance. Conclusions: We found that two distinct CD phenotypes have specific molecular signatures. Obtained results could direct improvement of current and development of new therapeutic strategies based on more specific molecular stratification of CD patients.",
publisher = "Elsevier Gmbh, Munich",
journal = "Pathology Research and Practice",
title = "Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy",
number = "6",
volume = "216",
doi = "10.1016/j.prp.2020.152945"
}
Stanković, B., Dragasević, S., Klaassen, K., Kotur, N., Srzentić Dražilov, S., Zukić, B., Sokic Milutinović, A., Milovanović, T., Lukić, S., Popović, D., Pavlović, S.,& Nikčević, G.. (2020). Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy. in Pathology Research and Practice
Elsevier Gmbh, Munich., 216(6).
https://doi.org/10.1016/j.prp.2020.152945
Stanković B, Dragasević S, Klaassen K, Kotur N, Srzentić Dražilov S, Zukić B, Sokic Milutinović A, Milovanović T, Lukić S, Popović D, Pavlović S, Nikčević G. Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy. in Pathology Research and Practice. 2020;216(6).
doi:10.1016/j.prp.2020.152945 .
Stanković, Biljana, Dragasević, Sanja, Klaassen, Kristel, Kotur, Nikola, Srzentić Dražilov, Sanja, Zukić, Branka, Sokic Milutinović, Aleksandra, Milovanović, Tamara, Lukić, Snežana, Popović, Dragan, Pavlović, Sonja, Nikčević, Gordana, "Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy" in Pathology Research and Practice, 216, no. 6 (2020),
https://doi.org/10.1016/j.prp.2020.152945 . .
3
2

Clinical Application of Thiopurine Pharmacogenomics in Pediatrics

Pavlović, Sonja; Kotur, Nikola; Stanković, Biljana; Gašić, Vladimir; Lucafo, Marianna; Decorti, Giuliana; Zukić, Branka

(Bentham Science Publ Ltd, Sharjah, 2020)

TY  - JOUR
AU  - Pavlović, Sonja
AU  - Kotur, Nikola
AU  - Stanković, Biljana
AU  - Gašić, Vladimir
AU  - Lucafo, Marianna
AU  - Decorti, Giuliana
AU  - Zukić, Branka
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1408
AB  - Background: Thiopurine drugs are used for the treatment of pediatric diseases. Inter-individual differences in the metabolism of these drugs greatly influence the risk of thiopurine induced toxicity and therapy failure. These differences are the consequence of genomic, epigenomic and transcriptomic variability among patients. Pharmacogenomics aims to individualize therapy according to the specific genetic signature of a patient. Treatment protocols based on thiopurine drugs have already been improved by applying pharmacogenomics in pediatric clinical practice. Objective: The aim of this review was to summarize the application of thiopurine pharmacogenomics in pediatric patients suffering from acute leukemias, different types of autoimmune and inflammatory diseases, as well as in posttransplant care. Methods: We searched PubMed/Medline database to identify thiopurine pharmacogenomic markers clinically relevant in pediatric diseases. Results: TPMT and NUDT15 pharmacogenomic testing is done in pediatric care, contributing to the reduction of thiopurine induced toxicity. Data on numerous novel potential pharmacogenomic markers relevant for optimization of thiopurine treatment are still controversial (ITPA, ABCC4, NT5C2, PRPS1, GSTM1, FTO gene variants). Majority of evidences regarding thiopurine pharmacogenomics in pediatrics have been acquired by studying acute lymphoblastic leukemia and inflammatory bowel disease. For other pediatric diseases, namely acute myeloid leukemia, non-Hodgkin lymphoma, juvenile idiopathic arthritis, atopic dermatitis, juvenile autoimmune hepatitis and renal allograft transplantation, data are still scarce. Conclusion: Thiopurine pharmacogenomics has shown to be one of the best examples of successful application of pharmacogenomics in pediatrics.
PB  - Bentham Science Publ Ltd, Sharjah
T2  - Current Drug Metabolism
T1  - Clinical Application of Thiopurine Pharmacogenomics in Pediatrics
EP  - 62
IS  - 1
SP  - 53
VL  - 21
DO  - 10.2174/1389200221666200303113456
ER  - 
@article{
author = "Pavlović, Sonja and Kotur, Nikola and Stanković, Biljana and Gašić, Vladimir and Lucafo, Marianna and Decorti, Giuliana and Zukić, Branka",
year = "2020",
abstract = "Background: Thiopurine drugs are used for the treatment of pediatric diseases. Inter-individual differences in the metabolism of these drugs greatly influence the risk of thiopurine induced toxicity and therapy failure. These differences are the consequence of genomic, epigenomic and transcriptomic variability among patients. Pharmacogenomics aims to individualize therapy according to the specific genetic signature of a patient. Treatment protocols based on thiopurine drugs have already been improved by applying pharmacogenomics in pediatric clinical practice. Objective: The aim of this review was to summarize the application of thiopurine pharmacogenomics in pediatric patients suffering from acute leukemias, different types of autoimmune and inflammatory diseases, as well as in posttransplant care. Methods: We searched PubMed/Medline database to identify thiopurine pharmacogenomic markers clinically relevant in pediatric diseases. Results: TPMT and NUDT15 pharmacogenomic testing is done in pediatric care, contributing to the reduction of thiopurine induced toxicity. Data on numerous novel potential pharmacogenomic markers relevant for optimization of thiopurine treatment are still controversial (ITPA, ABCC4, NT5C2, PRPS1, GSTM1, FTO gene variants). Majority of evidences regarding thiopurine pharmacogenomics in pediatrics have been acquired by studying acute lymphoblastic leukemia and inflammatory bowel disease. For other pediatric diseases, namely acute myeloid leukemia, non-Hodgkin lymphoma, juvenile idiopathic arthritis, atopic dermatitis, juvenile autoimmune hepatitis and renal allograft transplantation, data are still scarce. Conclusion: Thiopurine pharmacogenomics has shown to be one of the best examples of successful application of pharmacogenomics in pediatrics.",
publisher = "Bentham Science Publ Ltd, Sharjah",
journal = "Current Drug Metabolism",
title = "Clinical Application of Thiopurine Pharmacogenomics in Pediatrics",
pages = "62-53",
number = "1",
volume = "21",
doi = "10.2174/1389200221666200303113456"
}
Pavlović, S., Kotur, N., Stanković, B., Gašić, V., Lucafo, M., Decorti, G.,& Zukić, B.. (2020). Clinical Application of Thiopurine Pharmacogenomics in Pediatrics. in Current Drug Metabolism
Bentham Science Publ Ltd, Sharjah., 21(1), 53-62.
https://doi.org/10.2174/1389200221666200303113456
Pavlović S, Kotur N, Stanković B, Gašić V, Lucafo M, Decorti G, Zukić B. Clinical Application of Thiopurine Pharmacogenomics in Pediatrics. in Current Drug Metabolism. 2020;21(1):53-62.
doi:10.2174/1389200221666200303113456 .
Pavlović, Sonja, Kotur, Nikola, Stanković, Biljana, Gašić, Vladimir, Lucafo, Marianna, Decorti, Giuliana, Zukić, Branka, "Clinical Application of Thiopurine Pharmacogenomics in Pediatrics" in Current Drug Metabolism, 21, no. 1 (2020):53-62,
https://doi.org/10.2174/1389200221666200303113456 . .
1
6
6

Expression of miRNA-210 in human bone marrow-derived mesenchymal stromal cells under oxygen deprivation

Loncarić, Darija; Stanković, Biljana; Ghousein, Amani; Vreca, Misa; Spasovski, Vesna; Villacreces, Arnaud; Debeissat, Christelle; Grosset, Christophe F.; Ivanović, Zoran; Pavlović, Sonja

(Srpsko biološko društvo, Beograd, i dr., 2019)

TY  - JOUR
AU  - Loncarić, Darija
AU  - Stanković, Biljana
AU  - Ghousein, Amani
AU  - Vreca, Misa
AU  - Spasovski, Vesna
AU  - Villacreces, Arnaud
AU  - Debeissat, Christelle
AU  - Grosset, Christophe F.
AU  - Ivanović, Zoran
AU  - Pavlović, Sonja
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1263
AB  - A major limitation in the development of efficient clinical protocols for mesenchymal stromal cell (MStroC)-based tissue regeneration therapy is the low retention and survival of MStroC in injured tissue after therapeutic administration. Low oxygen concentration preconditioning (LOP) during ex vivo cultivation of MStroC, as a method for mimicking oxygenation in their physiological microenvironment, has been shown to be beneficial in clinical trials using MStroC. Introducing hypoxia-mimicking molecules into MStroC during cultivation could be an advantageous LOP strategy. MicroRNA (miRNA) drugs are good candidates for this approach. Analysis of the expression of miRNA-210 in human bone marrow-derived MStroC in conditions of acute and extended hypoxia (24 to 72 h) was performed using RT-qPCR methodology. HIF-1 alpha and HIF-2 alpha gene knockdown cell lines were generated using lentiviral transduction of short hairpin RNA (shRNA) in order to examine whether miRNA-210 expression is regulated by transcription factor HIF-1 and/or HIF-2. We detected a significant increase in miRNA-210 expression in hypoxic conditions at time points of 24, 48 and 72 h (p lt 0.05). Knocking down of HIF-1 alpha and HIF-2 alpha genes indicated involvement of both transcription factors in the elevation of miRNA-210 expression. These results point to miRNA-210 as a good candidate for a hypoxia-mimicking molecule in LOP strategy.
PB  - Srpsko biološko društvo, Beograd, i dr.
T2  - Archives of Biological Sciences
T1  - Expression of miRNA-210 in human bone marrow-derived mesenchymal stromal cells under oxygen deprivation
EP  - 208
IS  - 2
SP  - 201
VL  - 71
DO  - 10.2298/ABS181117001L
ER  - 
@article{
author = "Loncarić, Darija and Stanković, Biljana and Ghousein, Amani and Vreca, Misa and Spasovski, Vesna and Villacreces, Arnaud and Debeissat, Christelle and Grosset, Christophe F. and Ivanović, Zoran and Pavlović, Sonja",
year = "2019",
abstract = "A major limitation in the development of efficient clinical protocols for mesenchymal stromal cell (MStroC)-based tissue regeneration therapy is the low retention and survival of MStroC in injured tissue after therapeutic administration. Low oxygen concentration preconditioning (LOP) during ex vivo cultivation of MStroC, as a method for mimicking oxygenation in their physiological microenvironment, has been shown to be beneficial in clinical trials using MStroC. Introducing hypoxia-mimicking molecules into MStroC during cultivation could be an advantageous LOP strategy. MicroRNA (miRNA) drugs are good candidates for this approach. Analysis of the expression of miRNA-210 in human bone marrow-derived MStroC in conditions of acute and extended hypoxia (24 to 72 h) was performed using RT-qPCR methodology. HIF-1 alpha and HIF-2 alpha gene knockdown cell lines were generated using lentiviral transduction of short hairpin RNA (shRNA) in order to examine whether miRNA-210 expression is regulated by transcription factor HIF-1 and/or HIF-2. We detected a significant increase in miRNA-210 expression in hypoxic conditions at time points of 24, 48 and 72 h (p lt 0.05). Knocking down of HIF-1 alpha and HIF-2 alpha genes indicated involvement of both transcription factors in the elevation of miRNA-210 expression. These results point to miRNA-210 as a good candidate for a hypoxia-mimicking molecule in LOP strategy.",
publisher = "Srpsko biološko društvo, Beograd, i dr.",
journal = "Archives of Biological Sciences",
title = "Expression of miRNA-210 in human bone marrow-derived mesenchymal stromal cells under oxygen deprivation",
pages = "208-201",
number = "2",
volume = "71",
doi = "10.2298/ABS181117001L"
}
Loncarić, D., Stanković, B., Ghousein, A., Vreca, M., Spasovski, V., Villacreces, A., Debeissat, C., Grosset, C. F., Ivanović, Z.,& Pavlović, S.. (2019). Expression of miRNA-210 in human bone marrow-derived mesenchymal stromal cells under oxygen deprivation. in Archives of Biological Sciences
Srpsko biološko društvo, Beograd, i dr.., 71(2), 201-208.
https://doi.org/10.2298/ABS181117001L
Loncarić D, Stanković B, Ghousein A, Vreca M, Spasovski V, Villacreces A, Debeissat C, Grosset CF, Ivanović Z, Pavlović S. Expression of miRNA-210 in human bone marrow-derived mesenchymal stromal cells under oxygen deprivation. in Archives of Biological Sciences. 2019;71(2):201-208.
doi:10.2298/ABS181117001L .
Loncarić, Darija, Stanković, Biljana, Ghousein, Amani, Vreca, Misa, Spasovski, Vesna, Villacreces, Arnaud, Debeissat, Christelle, Grosset, Christophe F., Ivanović, Zoran, Pavlović, Sonja, "Expression of miRNA-210 in human bone marrow-derived mesenchymal stromal cells under oxygen deprivation" in Archives of Biological Sciences, 71, no. 2 (2019):201-208,
https://doi.org/10.2298/ABS181117001L . .
1
1

Ekspresioni obrazac duge nekodirajuće RNK growth arrest specific 5 u fazi indukcije u terapiji dečje akutne limfoblastne leukemije

Gašić, Vladimir; Stanković, Biljana; Zukić, Branka; Janić, Dragana; Dokmanović, Lidija; Krstovski, Nada; Lazić, Jelena; Milošević, Goran; Lucafò, Marianna; Stocco, Gabriele; Decorti, Giuliana; Pavlović, Sonja; Kotur, Nikola

(Društvo medicinskih biohemičara Srbije, Beograd i Versita, 2019)

TY  - JOUR
AU  - Gašić, Vladimir
AU  - Stanković, Biljana
AU  - Zukić, Branka
AU  - Janić, Dragana
AU  - Dokmanović, Lidija
AU  - Krstovski, Nada
AU  - Lazić, Jelena
AU  - Milošević, Goran
AU  - Lucafò, Marianna
AU  - Stocco, Gabriele
AU  - Decorti, Giuliana
AU  - Pavlović, Sonja
AU  - Kotur, Nikola
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1269
AB  - Uvod: Ekspresija duge nekodirajuće RNK G AS5 je izme - njena u mnogim kancerima zbog njene uloge u apoptozi i inhibiciji rasta ćelije. G AS5 interaguje sa glukokortikoidnim receptorom, što je čini potencijalnim farmakotranskripcionim markerom značajnim za glukokortikoidnu terapiju. Naš cilj u ovoj studiji je bio da analiziramo ekspresiju GAS5 tokom indukcione terapije kod dečje akutne limfoblastne leukemije (ALL), u kojoj se koriste glukokortikoidni lekovi, i da te rezultate povežemo sa odgovorom na terapiju. Metode: Nivo ekspresije G AS5 u mononuklearnim ćelijama periferne krvi izolovanih od 29 dece obolelih od ALL, određen je metodologijom RT-qPCR, i to u momentu dijagnoze, 15. i 33. dana indukcione terapije. Rezultati: Naši rezultati su pokazali da postoje interindivi - dualne razlike u ekspresiji GAS5 kod pacijenata, i to u svim analiziranim tačkama. Kod svakog ALL pacijenta GAS5 ekspresija je 15. dana bila visa u odnosu na ekspresiju u momentu dijagnoze (p  lt  0,0005). Nivo ekspresije GAS5 je 33. dana bio niži u poređenju sa 15. danom (p  lt  0,0005), ali je i dalje bio značajno visi u odnosu na momenat dijagnoze kod većine pacijenata (p = 0,001). Pacijenti čiji je broj blasta u perifernoj krvi 8. dana bio ispod 100 po mikrolitru periferne krvi, imali su viši nivo ekspresije GAS5 (p = 0,016) i niži odnos ekspresija merenih 15. dana i u momentu dijagnoze (p = 0,009). Zaključak: Nasi rezultati ukazuju da bi nivo ekspresije GAS5 mogao da bude marker terapijskog odgovora u indukcionoj terapiji kod dece obolele od ALL.
AB  - Background: Long non-coding RNA growth arrest-specific 5 (GAS5) is deregulated in many cancers because of its role in cell growth arrest and apoptosis. Additionally, GAS5 interacts with glucocorticoid receptor, making it a potential pharmacotranscription marker of glucocorticoid (GC) therapy. In this study, we aimed at analysing G AS5 expression in the remission induction therapy phase of childhood acute lymphoblastic leukemia (ALL), in which GCs are mandatorily used, and to correlate it with therapy response. Methods: G AS5 expression was measured in peripheral blood mononuclear cells taken from 29 childhood ALL patients at diagnosis, on day 15 and day 33 of remission induction therapy using RT-qPCR methodology. Results: Our results have shown interindividual differences in G AS5 expression at all time points. For each ALL patient, G A S5 expression was higher on day 15 in comparison to its level at diagnosis (p lt 0.0005). On day 33, the level of G A S5 expression decreased in comparison with day 15 (p lt 0.0005), but it was still significantly higher than at diagnosis for the majority of patients (p=0.001). Patients whose number of blasts on day 8 was below 100 per mL of peripheral blood had a higher GAS5 expression at diagnosis (p=0.016), and lower ratio day 15/diagnosis (p=0.009). Conclusions: Our results suggest that the expression level of GAS5 could be a potential marker of therapy response in remission induction therapy of childhood ALL.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Ekspresioni obrazac duge nekodirajuće RNK growth arrest specific 5 u fazi indukcije u terapiji dečje akutne limfoblastne leukemije
T1  - Expression pattern of long non-coding RNA growth arrest-specific 5 in the remission induction therapy in childhood acute lymphoblastic leukemia
EP  - 298
IS  - 3
SP  - 292
VL  - 38
DO  - 10.2478/jomb-2018-0038
ER  - 
@article{
author = "Gašić, Vladimir and Stanković, Biljana and Zukić, Branka and Janić, Dragana and Dokmanović, Lidija and Krstovski, Nada and Lazić, Jelena and Milošević, Goran and Lucafò, Marianna and Stocco, Gabriele and Decorti, Giuliana and Pavlović, Sonja and Kotur, Nikola",
year = "2019",
abstract = "Uvod: Ekspresija duge nekodirajuće RNK G AS5 je izme - njena u mnogim kancerima zbog njene uloge u apoptozi i inhibiciji rasta ćelije. G AS5 interaguje sa glukokortikoidnim receptorom, što je čini potencijalnim farmakotranskripcionim markerom značajnim za glukokortikoidnu terapiju. Naš cilj u ovoj studiji je bio da analiziramo ekspresiju GAS5 tokom indukcione terapije kod dečje akutne limfoblastne leukemije (ALL), u kojoj se koriste glukokortikoidni lekovi, i da te rezultate povežemo sa odgovorom na terapiju. Metode: Nivo ekspresije G AS5 u mononuklearnim ćelijama periferne krvi izolovanih od 29 dece obolelih od ALL, određen je metodologijom RT-qPCR, i to u momentu dijagnoze, 15. i 33. dana indukcione terapije. Rezultati: Naši rezultati su pokazali da postoje interindivi - dualne razlike u ekspresiji GAS5 kod pacijenata, i to u svim analiziranim tačkama. Kod svakog ALL pacijenta GAS5 ekspresija je 15. dana bila visa u odnosu na ekspresiju u momentu dijagnoze (p  lt  0,0005). Nivo ekspresije GAS5 je 33. dana bio niži u poređenju sa 15. danom (p  lt  0,0005), ali je i dalje bio značajno visi u odnosu na momenat dijagnoze kod većine pacijenata (p = 0,001). Pacijenti čiji je broj blasta u perifernoj krvi 8. dana bio ispod 100 po mikrolitru periferne krvi, imali su viši nivo ekspresije GAS5 (p = 0,016) i niži odnos ekspresija merenih 15. dana i u momentu dijagnoze (p = 0,009). Zaključak: Nasi rezultati ukazuju da bi nivo ekspresije GAS5 mogao da bude marker terapijskog odgovora u indukcionoj terapiji kod dece obolele od ALL., Background: Long non-coding RNA growth arrest-specific 5 (GAS5) is deregulated in many cancers because of its role in cell growth arrest and apoptosis. Additionally, GAS5 interacts with glucocorticoid receptor, making it a potential pharmacotranscription marker of glucocorticoid (GC) therapy. In this study, we aimed at analysing G AS5 expression in the remission induction therapy phase of childhood acute lymphoblastic leukemia (ALL), in which GCs are mandatorily used, and to correlate it with therapy response. Methods: G AS5 expression was measured in peripheral blood mononuclear cells taken from 29 childhood ALL patients at diagnosis, on day 15 and day 33 of remission induction therapy using RT-qPCR methodology. Results: Our results have shown interindividual differences in G AS5 expression at all time points. For each ALL patient, G A S5 expression was higher on day 15 in comparison to its level at diagnosis (p lt 0.0005). On day 33, the level of G A S5 expression decreased in comparison with day 15 (p lt 0.0005), but it was still significantly higher than at diagnosis for the majority of patients (p=0.001). Patients whose number of blasts on day 8 was below 100 per mL of peripheral blood had a higher GAS5 expression at diagnosis (p=0.016), and lower ratio day 15/diagnosis (p=0.009). Conclusions: Our results suggest that the expression level of GAS5 could be a potential marker of therapy response in remission induction therapy of childhood ALL.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Ekspresioni obrazac duge nekodirajuće RNK growth arrest specific 5 u fazi indukcije u terapiji dečje akutne limfoblastne leukemije, Expression pattern of long non-coding RNA growth arrest-specific 5 in the remission induction therapy in childhood acute lymphoblastic leukemia",
pages = "298-292",
number = "3",
volume = "38",
doi = "10.2478/jomb-2018-0038"
}
Gašić, V., Stanković, B., Zukić, B., Janić, D., Dokmanović, L., Krstovski, N., Lazić, J., Milošević, G., Lucafò, M., Stocco, G., Decorti, G., Pavlović, S.,& Kotur, N.. (2019). Ekspresioni obrazac duge nekodirajuće RNK growth arrest specific 5 u fazi indukcije u terapiji dečje akutne limfoblastne leukemije. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 38(3), 292-298.
https://doi.org/10.2478/jomb-2018-0038
Gašić V, Stanković B, Zukić B, Janić D, Dokmanović L, Krstovski N, Lazić J, Milošević G, Lucafò M, Stocco G, Decorti G, Pavlović S, Kotur N. Ekspresioni obrazac duge nekodirajuće RNK growth arrest specific 5 u fazi indukcije u terapiji dečje akutne limfoblastne leukemije. in Journal of Medical Biochemistry. 2019;38(3):292-298.
doi:10.2478/jomb-2018-0038 .
Gašić, Vladimir, Stanković, Biljana, Zukić, Branka, Janić, Dragana, Dokmanović, Lidija, Krstovski, Nada, Lazić, Jelena, Milošević, Goran, Lucafò, Marianna, Stocco, Gabriele, Decorti, Giuliana, Pavlović, Sonja, Kotur, Nikola, "Ekspresioni obrazac duge nekodirajuće RNK growth arrest specific 5 u fazi indukcije u terapiji dečje akutne limfoblastne leukemije" in Journal of Medical Biochemistry, 38, no. 3 (2019):292-298,
https://doi.org/10.2478/jomb-2018-0038 . .
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3
21