Rakićević, Ljiljana

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  • Rakićević, Ljiljana (54)

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DNA and RNA Molecules as a Foundation of Therapy Strategies for Treatment of Cardiovascular Diseases

Rakićević, Ljiljana

(2023)

TY  - JOUR
AU  - Rakićević, Ljiljana
PY  - 2023
UR  - https://www.mdpi.com/1999-4923/15/8/2141
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2192
AB  - There has always been a tendency of medicine to take an individualised approach to treating patients, but the most significant advances were achieved through the methods of molecular biology, where the nucleic acids are in the limelight. Decades of research of molecular biology resulted in setting medicine on a completely new platform. The most significant current research is related to the possibilities that DNA and RNA analyses can offer in terms of more precise diagnostics and more subtle stratification of patients in order to identify patients for specific therapy treatments. Additionally, principles of structure and functioning of nucleic acids have become a motive for creating entirely new therapy strategies and an innovative generation of drugs. All this also applies to cardiovascular diseases (CVDs) which are the leading cause of mortality in developed countries. This review considers the most up-to-date achievements related to the use of translatory potential of DNA and RNA in treatment of cardiovascular diseases, and considers the challenges and prospects in this field. The foundations which allow the use of translatory potential are also presented. The first part of this review focuses on the potential of the DNA variants which impact conventional therapies and on the DNA variants which are starting points for designing new pharmacotherapeutics. The second part of this review considers the translatory potential of non-coding RNA molecules which can be used to formulate new generations of therapeutics for CVDs.
T2  - Pharmaceutics
T2  - Pharmaceutics
T1  - DNA and RNA Molecules as a Foundation of Therapy Strategies for Treatment of Cardiovascular Diseases
IS  - 8
SP  - 2141
VL  - 15
DO  - 10.3390/pharmaceutics15082141
ER  - 
@article{
author = "Rakićević, Ljiljana",
year = "2023",
abstract = "There has always been a tendency of medicine to take an individualised approach to treating patients, but the most significant advances were achieved through the methods of molecular biology, where the nucleic acids are in the limelight. Decades of research of molecular biology resulted in setting medicine on a completely new platform. The most significant current research is related to the possibilities that DNA and RNA analyses can offer in terms of more precise diagnostics and more subtle stratification of patients in order to identify patients for specific therapy treatments. Additionally, principles of structure and functioning of nucleic acids have become a motive for creating entirely new therapy strategies and an innovative generation of drugs. All this also applies to cardiovascular diseases (CVDs) which are the leading cause of mortality in developed countries. This review considers the most up-to-date achievements related to the use of translatory potential of DNA and RNA in treatment of cardiovascular diseases, and considers the challenges and prospects in this field. The foundations which allow the use of translatory potential are also presented. The first part of this review focuses on the potential of the DNA variants which impact conventional therapies and on the DNA variants which are starting points for designing new pharmacotherapeutics. The second part of this review considers the translatory potential of non-coding RNA molecules which can be used to formulate new generations of therapeutics for CVDs.",
journal = "Pharmaceutics, Pharmaceutics",
title = "DNA and RNA Molecules as a Foundation of Therapy Strategies for Treatment of Cardiovascular Diseases",
number = "8",
pages = "2141",
volume = "15",
doi = "10.3390/pharmaceutics15082141"
}
Rakićević, L.. (2023). DNA and RNA Molecules as a Foundation of Therapy Strategies for Treatment of Cardiovascular Diseases. in Pharmaceutics, 15(8), 2141.
https://doi.org/10.3390/pharmaceutics15082141
Rakićević L. DNA and RNA Molecules as a Foundation of Therapy Strategies for Treatment of Cardiovascular Diseases. in Pharmaceutics. 2023;15(8):2141.
doi:10.3390/pharmaceutics15082141 .
Rakićević, Ljiljana, "DNA and RNA Molecules as a Foundation of Therapy Strategies for Treatment of Cardiovascular Diseases" in Pharmaceutics, 15, no. 8 (2023):2141,
https://doi.org/10.3390/pharmaceutics15082141 . .
1

Varijante gena "VKORC1" i "CYP2C9" kao farmakogenetički faktori u terapiji acenokumarolom kod bolesnika u Srbiji - razmatranje preosetljivosti i rezistencije

Rakićević, Ljiljana; Kovač, Mirjana; Radojković, Dragica; Radojković, Milica

(Srpsko lekarsko društvo, Beograd, 2022)

TY  - JOUR
AU  - Rakićević, Ljiljana
AU  - Kovač, Mirjana
AU  - Radojković, Dragica
AU  - Radojković, Milica
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1587
AB  - Uvod/Cilj Terapija kumarinima predstavlja jedan od najboljih modela za primenu farmakogenetike. Doprinos faktora koji utiču na terapiju kumarinima može značajno da varira između etničkih grupa, što opravdava sprovođenje studija specifičnih za populaciju. Cilj ove studije je bio da se analizira uticaj najvažnijih genetičkih faktora (geni VKORC1 i CYP2C9) koji utiču na terapiju kumarinima kod bolesnika iz Srbije. Metode Sprovedena je retrospektivna studija koja je obuhvatila 207 bolesnika na terapiji acenokumarolom. Genetičke analize su vršene direktnim sekvenciranjem. Analiziran je uticaj na dozu acenokumarola varijanti (VKORC1*2, CYP2C9*2, CYP2C9*3) koje izazivaju preosetljivost i varijanti gena VKORC1 koje izazivaju rezistenciju na kumarine. Višestruka regresiona analiza je korišćena u cilju dizajniranja matematičkog modela za predviđanje individualne doze leka na osnovu kliničko-demografskih i genetičkih podataka. Rezultati Studija je potvrdila značajan uticaj analiziranih genetičkih faktora na održavanje doze acenokumarola. Dizajniran je matematički model za predviđanje individualne doze acenokumarola i njegov nekorigovani R2 je bio 61,8. Prilikom testiranja, naš model je dao R2 vrednost od 42,6 i pokazao bolje predviđanje u poređenju sa modelom koji su dali drugi autori. Kod analiziranih bolesnika pronađeno je devet različitih varijanti u kodirajućem regionu gena VKORC1. Među nosiocima ovih varijanti 78% je bilo potpuno rezistentno, te nije bilo moguće postići terapeutski efekat čak ni sa visokim dozama acenokumarola. Zaključci Populacioni model za predviđanje individualne doze acenokumarola može pokazati prednosti u odnosu na modele koji se koriste na generalizovan način. Takođe, VKORC1 varijante koje izazivaju rezistenciju na kumarin treba uzeti u obzir prilikom planiranja terapije.
AB  - Introduction/Objective Coumarin therapy represents one of the best models for applying pharmacogenetics. The contribution of factors influencing coumarin therapy can vary significantly between ethnic groups, which justifies conducting population-specific studies. The aim of this study was to analyze the influence of the most important genetic factors (VKORC1 and CYP2C9 genes) that affect coumarin therapy in patients from Serbia. Methods A retrospective study involving 207 patients on acenocoumarol therapy was conducted. Genetic analyses were performed by direct sequencing. Influence on acenocoumarol dose of variants (VKORC1, CYP2C9*2, CYP2C9*3) causing hypersensitivity and VKORC1 variants causing resistance to acenocoumarol were analyzed. Multiple regression analysis was used to design a mathematical model for predicting individual drug dosage based on clinical-demographic and genetic data. Results The study confirmed significant influence of the analyzed genetic factors on acenocoumarol maintenance dose. We designed mathematical model for predicting individual acenocoumarol dose and its unadjusted R2 was 61.8. In the testing cohort, our model gave R2 value of 42.6 and showed better prediction in comparison with model given by other authors. In the analyzed patients, nine different variants in the VKORC1 coding region were found. Among carriers of these variants 78% were completely resistant, and it was not possible to achieve therapeutic effect even with high doses of acenocoumarol. Conclusions Population-specific model for prediction individual dose of acenocoumarol, may show advantages over protocols that are used in a generalized manner. Also, VKORC1 variants which cause coumarin resistance should be considered when planning therapy.
PB  - Srpsko lekarsko društvo, Beograd
T2  - Srpski arhiv za celokupno lekarstvo
T1  - Varijante gena "VKORC1" i "CYP2C9" kao farmakogenetički faktori u terapiji acenokumarolom kod bolesnika u Srbiji - razmatranje preosetljivosti i rezistencije
T1  - The 'VKORC1' and 'CYP2C9' gene variants as pharmacogenetic factors in acenocoumarol therapy in Serbian patients: Consideration of hypersensitivity and resistance
EP  - 162
IS  - 3-4
SP  - 156
VL  - 150
DO  - 10.2298/SARH211118013R
ER  - 
@article{
author = "Rakićević, Ljiljana and Kovač, Mirjana and Radojković, Dragica and Radojković, Milica",
year = "2022",
abstract = "Uvod/Cilj Terapija kumarinima predstavlja jedan od najboljih modela za primenu farmakogenetike. Doprinos faktora koji utiču na terapiju kumarinima može značajno da varira između etničkih grupa, što opravdava sprovođenje studija specifičnih za populaciju. Cilj ove studije je bio da se analizira uticaj najvažnijih genetičkih faktora (geni VKORC1 i CYP2C9) koji utiču na terapiju kumarinima kod bolesnika iz Srbije. Metode Sprovedena je retrospektivna studija koja je obuhvatila 207 bolesnika na terapiji acenokumarolom. Genetičke analize su vršene direktnim sekvenciranjem. Analiziran je uticaj na dozu acenokumarola varijanti (VKORC1*2, CYP2C9*2, CYP2C9*3) koje izazivaju preosetljivost i varijanti gena VKORC1 koje izazivaju rezistenciju na kumarine. Višestruka regresiona analiza je korišćena u cilju dizajniranja matematičkog modela za predviđanje individualne doze leka na osnovu kliničko-demografskih i genetičkih podataka. Rezultati Studija je potvrdila značajan uticaj analiziranih genetičkih faktora na održavanje doze acenokumarola. Dizajniran je matematički model za predviđanje individualne doze acenokumarola i njegov nekorigovani R2 je bio 61,8. Prilikom testiranja, naš model je dao R2 vrednost od 42,6 i pokazao bolje predviđanje u poređenju sa modelom koji su dali drugi autori. Kod analiziranih bolesnika pronađeno je devet različitih varijanti u kodirajućem regionu gena VKORC1. Među nosiocima ovih varijanti 78% je bilo potpuno rezistentno, te nije bilo moguće postići terapeutski efekat čak ni sa visokim dozama acenokumarola. Zaključci Populacioni model za predviđanje individualne doze acenokumarola može pokazati prednosti u odnosu na modele koji se koriste na generalizovan način. Takođe, VKORC1 varijante koje izazivaju rezistenciju na kumarin treba uzeti u obzir prilikom planiranja terapije., Introduction/Objective Coumarin therapy represents one of the best models for applying pharmacogenetics. The contribution of factors influencing coumarin therapy can vary significantly between ethnic groups, which justifies conducting population-specific studies. The aim of this study was to analyze the influence of the most important genetic factors (VKORC1 and CYP2C9 genes) that affect coumarin therapy in patients from Serbia. Methods A retrospective study involving 207 patients on acenocoumarol therapy was conducted. Genetic analyses were performed by direct sequencing. Influence on acenocoumarol dose of variants (VKORC1, CYP2C9*2, CYP2C9*3) causing hypersensitivity and VKORC1 variants causing resistance to acenocoumarol were analyzed. Multiple regression analysis was used to design a mathematical model for predicting individual drug dosage based on clinical-demographic and genetic data. Results The study confirmed significant influence of the analyzed genetic factors on acenocoumarol maintenance dose. We designed mathematical model for predicting individual acenocoumarol dose and its unadjusted R2 was 61.8. In the testing cohort, our model gave R2 value of 42.6 and showed better prediction in comparison with model given by other authors. In the analyzed patients, nine different variants in the VKORC1 coding region were found. Among carriers of these variants 78% were completely resistant, and it was not possible to achieve therapeutic effect even with high doses of acenocoumarol. Conclusions Population-specific model for prediction individual dose of acenocoumarol, may show advantages over protocols that are used in a generalized manner. Also, VKORC1 variants which cause coumarin resistance should be considered when planning therapy.",
publisher = "Srpsko lekarsko društvo, Beograd",
journal = "Srpski arhiv za celokupno lekarstvo",
title = "Varijante gena "VKORC1" i "CYP2C9" kao farmakogenetički faktori u terapiji acenokumarolom kod bolesnika u Srbiji - razmatranje preosetljivosti i rezistencije, The 'VKORC1' and 'CYP2C9' gene variants as pharmacogenetic factors in acenocoumarol therapy in Serbian patients: Consideration of hypersensitivity and resistance",
pages = "162-156",
number = "3-4",
volume = "150",
doi = "10.2298/SARH211118013R"
}
Rakićević, L., Kovač, M., Radojković, D.,& Radojković, M.. (2022). Varijante gena "VKORC1" i "CYP2C9" kao farmakogenetički faktori u terapiji acenokumarolom kod bolesnika u Srbiji - razmatranje preosetljivosti i rezistencije. in Srpski arhiv za celokupno lekarstvo
Srpsko lekarsko društvo, Beograd., 150(3-4), 156-162.
https://doi.org/10.2298/SARH211118013R
Rakićević L, Kovač M, Radojković D, Radojković M. Varijante gena "VKORC1" i "CYP2C9" kao farmakogenetički faktori u terapiji acenokumarolom kod bolesnika u Srbiji - razmatranje preosetljivosti i rezistencije. in Srpski arhiv za celokupno lekarstvo. 2022;150(3-4):156-162.
doi:10.2298/SARH211118013R .
Rakićević, Ljiljana, Kovač, Mirjana, Radojković, Dragica, Radojković, Milica, "Varijante gena "VKORC1" i "CYP2C9" kao farmakogenetički faktori u terapiji acenokumarolom kod bolesnika u Srbiji - razmatranje preosetljivosti i rezistencije" in Srpski arhiv za celokupno lekarstvo, 150, no. 3-4 (2022):156-162,
https://doi.org/10.2298/SARH211118013R . .
1

Matrix metalloproteinase-2 (MMP-2) and-9 (MMP-9) gene variants and microvascular complications in type 2 diabetes patients

Andjelic, Jelic M.; Radojković, Dragica; Nikolić, Aleksandra; Rakićević, Ljiljana; Babić, Tamara; Jelic, D.; Lalic, N. M.

(Sciendo, 2022)

TY  - JOUR
AU  - Andjelic, Jelic M.
AU  - Radojković, Dragica
AU  - Nikolić, Aleksandra
AU  - Rakićević, Ljiljana
AU  - Babić, Tamara
AU  - Jelic, D.
AU  - Lalic, N. M.
PY  - 2022
UR  - https://sciendo.com/article/10.2478/bjmg-2022-0001
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1787
AB  - AbstractVascular complications are the leading cause of increased morbidity and mortality of diabetic patients. It has been postulated that matrix metalloproteinases MMP-2 and MMP-9, zinc-dependent endopeptidases through remodeling of the extracellular matrix, can contribute to the onset and progression of diabetic vascular complications. The aim of our study was to assess whether there is a major difference in single nucleotide polymorphisms in the MMP-2 (at position -1306C˃T) and MMP-9 (at position -1562C˃T) gene in type 2 diabetic patients and healthy controls and to determine whether there is an association of these gene variants with the presence of microvascular complications in diabetic patients. Our study included 102 type 2 diabetes patients and a control group which was comprised of 56 healthy controls. All diabetic patients were screened for microvascular diabetes complications. Genotypes were detected by polymerase chain reactions followed by restriction analyses with specific endonucleases and their frequencies were determined. The MMP-2 variant -1306C>T showed a negative correlation with type 2 diabetes (p=0.028). It was also shown that the presence of the -1306C allele increases the probability of developing type 2 diabetes. This was a 2.2 fold increase and that the -1306 T allele has a protective role in regards to
PB  - Sciendo
T2  - Balkan Journal of Medical Genetics
T2  - Balkan Journal of Medical Genetics
T1  - Matrix metalloproteinase-2 (MMP-2) and-9 (MMP-9) gene variants and microvascular complications in type 2 diabetes patients
EP  - 40
IS  - 1
SP  - 35
VL  - 25
DO  - 10.2478/bjmg-2022-0001
ER  - 
@article{
author = "Andjelic, Jelic M. and Radojković, Dragica and Nikolić, Aleksandra and Rakićević, Ljiljana and Babić, Tamara and Jelic, D. and Lalic, N. M.",
year = "2022",
abstract = "AbstractVascular complications are the leading cause of increased morbidity and mortality of diabetic patients. It has been postulated that matrix metalloproteinases MMP-2 and MMP-9, zinc-dependent endopeptidases through remodeling of the extracellular matrix, can contribute to the onset and progression of diabetic vascular complications. The aim of our study was to assess whether there is a major difference in single nucleotide polymorphisms in the MMP-2 (at position -1306C˃T) and MMP-9 (at position -1562C˃T) gene in type 2 diabetic patients and healthy controls and to determine whether there is an association of these gene variants with the presence of microvascular complications in diabetic patients. Our study included 102 type 2 diabetes patients and a control group which was comprised of 56 healthy controls. All diabetic patients were screened for microvascular diabetes complications. Genotypes were detected by polymerase chain reactions followed by restriction analyses with specific endonucleases and their frequencies were determined. The MMP-2 variant -1306C>T showed a negative correlation with type 2 diabetes (p=0.028). It was also shown that the presence of the -1306C allele increases the probability of developing type 2 diabetes. This was a 2.2 fold increase and that the -1306 T allele has a protective role in regards to",
publisher = "Sciendo",
journal = "Balkan Journal of Medical Genetics, Balkan Journal of Medical Genetics",
title = "Matrix metalloproteinase-2 (MMP-2) and-9 (MMP-9) gene variants and microvascular complications in type 2 diabetes patients",
pages = "40-35",
number = "1",
volume = "25",
doi = "10.2478/bjmg-2022-0001"
}
Andjelic, J. M., Radojković, D., Nikolić, A., Rakićević, L., Babić, T., Jelic, D.,& Lalic, N. M.. (2022). Matrix metalloproteinase-2 (MMP-2) and-9 (MMP-9) gene variants and microvascular complications in type 2 diabetes patients. in Balkan Journal of Medical Genetics
Sciendo., 25(1), 35-40.
https://doi.org/10.2478/bjmg-2022-0001
Andjelic JM, Radojković D, Nikolić A, Rakićević L, Babić T, Jelic D, Lalic NM. Matrix metalloproteinase-2 (MMP-2) and-9 (MMP-9) gene variants and microvascular complications in type 2 diabetes patients. in Balkan Journal of Medical Genetics. 2022;25(1):35-40.
doi:10.2478/bjmg-2022-0001 .
Andjelic, Jelic M., Radojković, Dragica, Nikolić, Aleksandra, Rakićević, Ljiljana, Babić, Tamara, Jelic, D., Lalic, N. M., "Matrix metalloproteinase-2 (MMP-2) and-9 (MMP-9) gene variants and microvascular complications in type 2 diabetes patients" in Balkan Journal of Medical Genetics, 25, no. 1 (2022):35-40,
https://doi.org/10.2478/bjmg-2022-0001 . .

Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy

Bačković, Dragana; Novković, Mirjana; Matić, Dragan; Antonijević, Nebojša; Strugarević, Evgenija; Kovač, Mirjana; Kušić-Tišma, Jelena; Rakićević, Ljiljana; Radojković, Dragica

(Beograd : Udruženje kardiologa Srbije, 2021)

TY  - CONF
AU  - Bačković, Dragana
AU  - Novković, Mirjana
AU  - Matić, Dragan
AU  - Antonijević, Nebojša
AU  - Strugarević, Evgenija
AU  - Kovač, Mirjana
AU  - Kušić-Tišma, Jelena
AU  - Rakićević, Ljiljana
AU  - Radojković, Dragica
PY  - 2021
UR  - https://www.uksrb.rs/en/magazine/archive/heart-and-blood-vessels-number-32021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2344
AB  - Introduction. Despite proven clinical effect of clopidogrel, a
considerable number of patients do not have an adequate
response to this type of medication. Problems during therapy occur in the form of resistance, which is present in 11%
of patients or bleeding that occurs in about 9% of patients.
Pharmacogenomics studies demonstrated that variants of
the CYP2C19 gene significantly influence the interindividual heterogenity of the clopidogrel response. The American
Heart Association, US Food and Drug Administration and the
European Medicines Agency, cite the CYP2C19 gene as a significant factor which influences patients response to clopidogrel. Further, it has been shown that the contribution of
genetic and non-genetic factors affecting clopidogrel therapy
may vary between patients from different populations, which
justifies conducting population-specific studies.
The aim. The aim of our study was to examine the significance
of the CYP2C19*2 and the CYP2C19*17 variants in the individual response to clopidogrel, in Serbian patients.
Methods. The study involved 108 patients with carotid artery
stenosis who underwent endarterectomy and received clopidogrel for at least 30 days after the intervention. Also, 120
patients with myocardial infarction receiving clopidogrel after PCI (percutaneous coronary intervention) were included.
Commercial tests were used for standard laboratory testing.
Allelic discrimination was performed after Sanger sequencing.
Results were analysed using statistical tests.
Results. In patients undergoing endarterectomy CYP2C19*2
carriers had a higher risk for being clopidogrel low-responder
in comparison with non-carriers (1.250, 95% CI 1.695–1.658,
P<0.01). In the group of patients undergoing PCI, risk for reinfarction in patients who were carriers of CYP2C19*2 was higher
compared to patients with wild type genotype (OR 5.355, 95%
CI 0.955-31.08; P=0.038). Variant CYP2C19*17 showed no association with variations in response to clopidogrel therapy.
Conclusion. The CYP2C19*2 variant shows significant association with a poor response to clopidogrel and it should be
considered when planning therapy.
PB  - Beograd : Udruženje kardiologa Srbije
C3  - Heart and Blood Vessels
T1  - Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy
IS  - 3
VL  - 40
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2344
ER  - 
@conference{
author = "Bačković, Dragana and Novković, Mirjana and Matić, Dragan and Antonijević, Nebojša and Strugarević, Evgenija and Kovač, Mirjana and Kušić-Tišma, Jelena and Rakićević, Ljiljana and Radojković, Dragica",
year = "2021",
abstract = "Introduction. Despite proven clinical effect of clopidogrel, a
considerable number of patients do not have an adequate
response to this type of medication. Problems during therapy occur in the form of resistance, which is present in 11%
of patients or bleeding that occurs in about 9% of patients.
Pharmacogenomics studies demonstrated that variants of
the CYP2C19 gene significantly influence the interindividual heterogenity of the clopidogrel response. The American
Heart Association, US Food and Drug Administration and the
European Medicines Agency, cite the CYP2C19 gene as a significant factor which influences patients response to clopidogrel. Further, it has been shown that the contribution of
genetic and non-genetic factors affecting clopidogrel therapy
may vary between patients from different populations, which
justifies conducting population-specific studies.
The aim. The aim of our study was to examine the significance
of the CYP2C19*2 and the CYP2C19*17 variants in the individual response to clopidogrel, in Serbian patients.
Methods. The study involved 108 patients with carotid artery
stenosis who underwent endarterectomy and received clopidogrel for at least 30 days after the intervention. Also, 120
patients with myocardial infarction receiving clopidogrel after PCI (percutaneous coronary intervention) were included.
Commercial tests were used for standard laboratory testing.
Allelic discrimination was performed after Sanger sequencing.
Results were analysed using statistical tests.
Results. In patients undergoing endarterectomy CYP2C19*2
carriers had a higher risk for being clopidogrel low-responder
in comparison with non-carriers (1.250, 95% CI 1.695–1.658,
P<0.01). In the group of patients undergoing PCI, risk for reinfarction in patients who were carriers of CYP2C19*2 was higher
compared to patients with wild type genotype (OR 5.355, 95%
CI 0.955-31.08; P=0.038). Variant CYP2C19*17 showed no association with variations in response to clopidogrel therapy.
Conclusion. The CYP2C19*2 variant shows significant association with a poor response to clopidogrel and it should be
considered when planning therapy.",
publisher = "Beograd : Udruženje kardiologa Srbije",
journal = "Heart and Blood Vessels",
title = "Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy",
number = "3",
volume = "40",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2344"
}
Bačković, D., Novković, M., Matić, D., Antonijević, N., Strugarević, E., Kovač, M., Kušić-Tišma, J., Rakićević, L.,& Radojković, D.. (2021). Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy. in Heart and Blood Vessels
Beograd : Udruženje kardiologa Srbije., 40(3).
https://hdl.handle.net/21.15107/rcub_imagine_2344
Bačković D, Novković M, Matić D, Antonijević N, Strugarević E, Kovač M, Kušić-Tišma J, Rakićević L, Radojković D. Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy. in Heart and Blood Vessels. 2021;40(3).
https://hdl.handle.net/21.15107/rcub_imagine_2344 .
Bačković, Dragana, Novković, Mirjana, Matić, Dragan, Antonijević, Nebojša, Strugarević, Evgenija, Kovač, Mirjana, Kušić-Tišma, Jelena, Rakićević, Ljiljana, Radojković, Dragica, "Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy" in Heart and Blood Vessels, 40, no. 3 (2021),
https://hdl.handle.net/21.15107/rcub_imagine_2344 .

Non-coding RNAs as a prospect in diagnostics and treatment of cardiovascular diseases

Rakićević, Ljiljana

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

TY  - CHAP
AU  - Rakićević, Ljiljana
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1718
AB  - Kardiovaskularne bolesti (KVB) su klasa oboljenja koja obuhvataju srce i/ili krvne sudove i nastaju složenim
sadejstvom genetičkih i stečenih faktora. Razvoj molekularne biologije omogućio je nove uvide u fundamentalne
mehanizme koji dovode do KVB, kao i napredak u dijagnostici, prognostici i lečenju. Novi pristupi
u dijagnostici i lečenju KVB podstaknuti su istraživanjima koja se odnose na nekodirajuće RNK - duge nekodirajuće
RNK i kratke nekodirajuće RNK. Ova klasa molekula, ne samo da se povezuje sa različitim mehanizmima
koji dovode do razvoja KVB, nego se prepoznaje njihov potencijal kao biomarkera,
farmakogenetičkih faktora, novih meta lekova i novih alatki u lečenju bolesti. Upotreba nekih od njih u lečenju
ljudi je i odobrena od strane relevantnih agencija. Posebnu pažnju privlače studije koje se odnose na
nekodirajuće RNK poreklom iz ekstracelularnih vezikula, dodatno potvrđujući potencijal nekodirajuće RNK
kao leka budućnosti, ne samo u tretmanu KVB.
AB  - Cardiovascular diseases (CVDs) are group of diseases which encompass heart and/or blood vessels and they
originate from complex coaction of genetic and acquired factors. Development of molecular biology has enabled
new insights into fundamental mechanisms which lead to CVDs, as well as progress in diagnostics,
prognosis and treatment. New approaches to diagnostics and treatment of CVDs have been encouraged
by researches which are related to non-coding RNA, long non-coding and short non-coding RNA. Not only
is this group of molecules being associated with different mechanisms which lead to CVDs, but their potential
to be biomarkers, pharmacogenetic factors, new drug targets and new treatment tools is being recognised.
Relevant agencies have approved some of them to be used for human treatments. Studies related to
non-coding RNAs deriving from extracellular vesicles are getting special attention, additionally confirming
non-coding RNAs potential as drug of the future, not limited just to CVDs.
PB  - Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo
T2  - Trendovi u molekularnoj Biologiji
T1  - Non-coding RNAs as a prospect in diagnostics and treatment of cardiovascular diseases
T1  - Nekodirajuće RNK kao perspektiva u dijagnostici i lečenju kardiovaskularnih bolesti
EP  - 151
SP  - 146
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1718
ER  - 
@inbook{
author = "Rakićević, Ljiljana",
year = "2021",
abstract = "Kardiovaskularne bolesti (KVB) su klasa oboljenja koja obuhvataju srce i/ili krvne sudove i nastaju složenim
sadejstvom genetičkih i stečenih faktora. Razvoj molekularne biologije omogućio je nove uvide u fundamentalne
mehanizme koji dovode do KVB, kao i napredak u dijagnostici, prognostici i lečenju. Novi pristupi
u dijagnostici i lečenju KVB podstaknuti su istraživanjima koja se odnose na nekodirajuće RNK - duge nekodirajuće
RNK i kratke nekodirajuće RNK. Ova klasa molekula, ne samo da se povezuje sa različitim mehanizmima
koji dovode do razvoja KVB, nego se prepoznaje njihov potencijal kao biomarkera,
farmakogenetičkih faktora, novih meta lekova i novih alatki u lečenju bolesti. Upotreba nekih od njih u lečenju
ljudi je i odobrena od strane relevantnih agencija. Posebnu pažnju privlače studije koje se odnose na
nekodirajuće RNK poreklom iz ekstracelularnih vezikula, dodatno potvrđujući potencijal nekodirajuće RNK
kao leka budućnosti, ne samo u tretmanu KVB., Cardiovascular diseases (CVDs) are group of diseases which encompass heart and/or blood vessels and they
originate from complex coaction of genetic and acquired factors. Development of molecular biology has enabled
new insights into fundamental mechanisms which lead to CVDs, as well as progress in diagnostics,
prognosis and treatment. New approaches to diagnostics and treatment of CVDs have been encouraged
by researches which are related to non-coding RNA, long non-coding and short non-coding RNA. Not only
is this group of molecules being associated with different mechanisms which lead to CVDs, but their potential
to be biomarkers, pharmacogenetic factors, new drug targets and new treatment tools is being recognised.
Relevant agencies have approved some of them to be used for human treatments. Studies related to
non-coding RNAs deriving from extracellular vesicles are getting special attention, additionally confirming
non-coding RNAs potential as drug of the future, not limited just to CVDs.",
publisher = "Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo",
journal = "Trendovi u molekularnoj Biologiji",
booktitle = "Non-coding RNAs as a prospect in diagnostics and treatment of cardiovascular diseases, Nekodirajuće RNK kao perspektiva u dijagnostici i lečenju kardiovaskularnih bolesti",
pages = "151-146",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1718"
}
Rakićević, L.. (2021). Non-coding RNAs as a prospect in diagnostics and treatment of cardiovascular diseases. in Trendovi u molekularnoj Biologiji
Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo., 146-151.
https://hdl.handle.net/21.15107/rcub_imagine_1718
Rakićević L. Non-coding RNAs as a prospect in diagnostics and treatment of cardiovascular diseases. in Trendovi u molekularnoj Biologiji. 2021;:146-151.
https://hdl.handle.net/21.15107/rcub_imagine_1718 .
Rakićević, Ljiljana, "Non-coding RNAs as a prospect in diagnostics and treatment of cardiovascular diseases" in Trendovi u molekularnoj Biologiji (2021):146-151,
https://hdl.handle.net/21.15107/rcub_imagine_1718 .

Pharmacogenetics of Clopidogrel Therapy and Neurointerventional Procedures: We Need Precision Data for Precision Medicine

Rakićević, Ljiljana; Nestorović, Aleksandra

(Wiley, Hoboken, 2019)

TY  - JOUR
AU  - Rakićević, Ljiljana
AU  - Nestorović, Aleksandra
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1277
AB  - Genetics has given a real boost to personalized and precision medicine, providing data used either for precise diagnostics, prediction of the course of illness, or for selecting therapy and tailoring it. Pharmacogenetics, as a discipline researching connection between genetic background of an individual and the effect of a certain drug, has created new possibilities in medicine. One of the most researched drugs in pharmacogenetics is certainly clopidogrel.
PB  - Wiley, Hoboken
T2  - Clinical Pharmacology & Therapeutics
T1  - Pharmacogenetics of Clopidogrel Therapy and Neurointerventional Procedures: We Need Precision Data for Precision Medicine
EP  - 549
IS  - 3
SP  - 547
VL  - 105
DO  - 10.1002/cpt.1105
ER  - 
@article{
author = "Rakićević, Ljiljana and Nestorović, Aleksandra",
year = "2019",
abstract = "Genetics has given a real boost to personalized and precision medicine, providing data used either for precise diagnostics, prediction of the course of illness, or for selecting therapy and tailoring it. Pharmacogenetics, as a discipline researching connection between genetic background of an individual and the effect of a certain drug, has created new possibilities in medicine. One of the most researched drugs in pharmacogenetics is certainly clopidogrel.",
publisher = "Wiley, Hoboken",
journal = "Clinical Pharmacology & Therapeutics",
title = "Pharmacogenetics of Clopidogrel Therapy and Neurointerventional Procedures: We Need Precision Data for Precision Medicine",
pages = "549-547",
number = "3",
volume = "105",
doi = "10.1002/cpt.1105"
}
Rakićević, L.,& Nestorović, A.. (2019). Pharmacogenetics of Clopidogrel Therapy and Neurointerventional Procedures: We Need Precision Data for Precision Medicine. in Clinical Pharmacology & Therapeutics
Wiley, Hoboken., 105(3), 547-549.
https://doi.org/10.1002/cpt.1105
Rakićević L, Nestorović A. Pharmacogenetics of Clopidogrel Therapy and Neurointerventional Procedures: We Need Precision Data for Precision Medicine. in Clinical Pharmacology & Therapeutics. 2019;105(3):547-549.
doi:10.1002/cpt.1105 .
Rakićević, Ljiljana, Nestorović, Aleksandra, "Pharmacogenetics of Clopidogrel Therapy and Neurointerventional Procedures: We Need Precision Data for Precision Medicine" in Clinical Pharmacology & Therapeutics, 105, no. 3 (2019):547-549,
https://doi.org/10.1002/cpt.1105 . .
1
4
2
4

Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel

Novković, Mirjana; Matić, Dragan; Kušić-Tišma, Jelena; Antonijević, Nebojša; Radojković, Dragica; Rakićević, Ljiljana

(Springer Heidelberg, Heidelberg, 2018)

TY  - JOUR
AU  - Novković, Mirjana
AU  - Matić, Dragan
AU  - Kušić-Tišma, Jelena
AU  - Antonijević, Nebojša
AU  - Radojković, Dragica
AU  - Rakićević, Ljiljana
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1187
AB  - Bleeding is one of the possible adverse events during clopidogrel therapy. The CYP2C19 gene is the most significant genetic factor which influences response to clopidogrel treatment. We aimed to examine the contribution of the CYP2C19 gene to bleeding occurrence during clopidogrel therapy in Serbian patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). This case-control study included 53 patients who experienced bleeding and 55 patients without bleeding. Bleeding events were defined and classified using the Bleeding Academic Research Consortium (BARC) criteria. All patients were prescribed daily doses of clopidogrel during the 1-year follow-up after PCI. The CYP2C19*17 (c.-806C  gt  T, rs12248560), rs11568732 (c.-889T  gt  G, CYP2C19*20), CYP2C19*2 (c.681G  gt  A; rs4244285) and CYP2C19*3 (c.636G  gt  A; rs4986893) variants were analysed in all 108 patients. Additionally, sequencing of all nine exons, 5'UTR and 3'UTR in the rs11568732 carriers was performed. Association between bleeding (BARC type ae lt yen gt  2) and the CYP2C19*17 variant was not observed [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.2-1.1; p = 0.107). The rs11568732 variant showed significant association with bleeding (OR, 3.7; 95% CI, 1.12-12.44; p = 0.025). Also, we found that the rs11568732 variant appears independently of haplotype CYP2C19*3B, which is contrary to the previous findings. Our results indicate the absence of CYP2C19*17 influence and turn the attention to the potential significance of the rs11568732 variant in terms of adverse effects of clopidogrel. However, it is necessary to conduct an independent conformation study in order to verify this finding. Also, an analysis of the functional implication of the rs11568732 variant is necessary in order to confirm the significance of this variant, both in relation to its influence on gene expression and in relation to its medical significance.
PB  - Springer Heidelberg, Heidelberg
T2  - European Journal of Clinical Pharmacology
T1  - Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel
EP  - 451
IS  - 4
SP  - 443
VL  - 74
DO  - 10.1007/s00228-017-2401-5
ER  - 
@article{
author = "Novković, Mirjana and Matić, Dragan and Kušić-Tišma, Jelena and Antonijević, Nebojša and Radojković, Dragica and Rakićević, Ljiljana",
year = "2018",
abstract = "Bleeding is one of the possible adverse events during clopidogrel therapy. The CYP2C19 gene is the most significant genetic factor which influences response to clopidogrel treatment. We aimed to examine the contribution of the CYP2C19 gene to bleeding occurrence during clopidogrel therapy in Serbian patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). This case-control study included 53 patients who experienced bleeding and 55 patients without bleeding. Bleeding events were defined and classified using the Bleeding Academic Research Consortium (BARC) criteria. All patients were prescribed daily doses of clopidogrel during the 1-year follow-up after PCI. The CYP2C19*17 (c.-806C  gt  T, rs12248560), rs11568732 (c.-889T  gt  G, CYP2C19*20), CYP2C19*2 (c.681G  gt  A; rs4244285) and CYP2C19*3 (c.636G  gt  A; rs4986893) variants were analysed in all 108 patients. Additionally, sequencing of all nine exons, 5'UTR and 3'UTR in the rs11568732 carriers was performed. Association between bleeding (BARC type ae lt yen gt  2) and the CYP2C19*17 variant was not observed [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.2-1.1; p = 0.107). The rs11568732 variant showed significant association with bleeding (OR, 3.7; 95% CI, 1.12-12.44; p = 0.025). Also, we found that the rs11568732 variant appears independently of haplotype CYP2C19*3B, which is contrary to the previous findings. Our results indicate the absence of CYP2C19*17 influence and turn the attention to the potential significance of the rs11568732 variant in terms of adverse effects of clopidogrel. However, it is necessary to conduct an independent conformation study in order to verify this finding. Also, an analysis of the functional implication of the rs11568732 variant is necessary in order to confirm the significance of this variant, both in relation to its influence on gene expression and in relation to its medical significance.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "European Journal of Clinical Pharmacology",
title = "Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel",
pages = "451-443",
number = "4",
volume = "74",
doi = "10.1007/s00228-017-2401-5"
}
Novković, M., Matić, D., Kušić-Tišma, J., Antonijević, N., Radojković, D.,& Rakićević, L.. (2018). Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel. in European Journal of Clinical Pharmacology
Springer Heidelberg, Heidelberg., 74(4), 443-451.
https://doi.org/10.1007/s00228-017-2401-5
Novković M, Matić D, Kušić-Tišma J, Antonijević N, Radojković D, Rakićević L. Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel. in European Journal of Clinical Pharmacology. 2018;74(4):443-451.
doi:10.1007/s00228-017-2401-5 .
Novković, Mirjana, Matić, Dragan, Kušić-Tišma, Jelena, Antonijević, Nebojša, Radojković, Dragica, Rakićević, Ljiljana, "Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel" in European Journal of Clinical Pharmacology, 74, no. 4 (2018):443-451,
https://doi.org/10.1007/s00228-017-2401-5 . .
9
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8

Economic analysis of pharmacogenomic-guided clopidogrel treatment in Serbian patients with myocardial infarction undergoing primary percutaneous coronary intervention

Mitropoulou, Christina; Fragoulakis, Vasilios; Rakićević, Ljiljana; Novković, Mirjana; Vozikis, Athanassios; Matić, Dragan M.; Antonijević, Nebojša; Radojković, Dragica ; van Schaik, Ron H.; Patrinos, George P.

(Future Medicine Ltd, London, 2016)

TY  - JOUR
AU  - Mitropoulou, Christina
AU  - Fragoulakis, Vasilios
AU  - Rakićević, Ljiljana
AU  - Novković, Mirjana
AU  - Vozikis, Athanassios
AU  - Matić, Dragan M.
AU  - Antonijević, Nebojša
AU  - Radojković, Dragica 
AU  - van Schaik, Ron H.
AU  - Patrinos, George P.
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/965
AB  - Introduction: Clopidogrel, which is activated by the CYP2C19 enzyme, is among the drugs for which all major regulatory agencies recommend genetic testing to be performed to identify a patient's CYP2C19 genotype in order to determine the optimal antiplatelet therapeutic scheme. The CYP2C19*2 and CYP2C19*3 variants are loss-of-function alleles, leading to abolished CYP2C19 function and thus have the risk of thrombotic events for carriers of these alleles on standard dosages, while the CYP2C19*17 allele results in CYP2C19 hyperactivity. Aims: Here, we report our findings from a retrospective study to assess whether genotyping for the CYP2C19*2 allele was cost effective for myocardial infarction patients receiving clopidogrel treatment in the Serbian population compared with the nongenotype-guided treatment. Results: We found that 59.3% of the CYP2C19*1/*1 patients had a minor or major bleeding event versus 42.85% of the CYP2C19*1/*2 and *2/*2, while a reinfarction event occurred only in 2.3% of the CYP21C9*1/*1 patients, compared with 11.2% of the CYP2C19*1/*2 and CYP2C19*2/*2 patients. There were subtle differences between the two patient groups, as far as the duration of hospitalization and rehabilitation is concerned, in favor of the CYP2C19*1/*1 group. The mean cost for the CYP2C19*1/*1 patients was estimated at (sic)2547 versus (sic)2799 in the CYP2C19*1/*2 and CYP2C19*2/*2 patients. Furthermore, based on the overall CYP2C19*1/*2 genotype frequencies in the Serbian population, a break-even point analysis indicated that performing the genetic test prior to drug prescription represents a cost-saving option, saving (sic)13 per person on average. Conclusion: Overall, our data demonstrate that pharmacogenomics-guided clopidogrel treatment may represent a cost-saving approach for the management of myocardial infarction patients undergoing primary percutaneous coronary intervention in Serbia.
PB  - Future Medicine Ltd, London
T2  - Pharmacogenomics
T1  - Economic analysis of pharmacogenomic-guided clopidogrel treatment in Serbian patients with myocardial infarction undergoing primary percutaneous coronary intervention
EP  - 1784
IS  - 16
SP  - 1775
VL  - 17
DO  - 10.2217/pgs-2016-0052
ER  - 
@article{
author = "Mitropoulou, Christina and Fragoulakis, Vasilios and Rakićević, Ljiljana and Novković, Mirjana and Vozikis, Athanassios and Matić, Dragan M. and Antonijević, Nebojša and Radojković, Dragica  and van Schaik, Ron H. and Patrinos, George P.",
year = "2016",
abstract = "Introduction: Clopidogrel, which is activated by the CYP2C19 enzyme, is among the drugs for which all major regulatory agencies recommend genetic testing to be performed to identify a patient's CYP2C19 genotype in order to determine the optimal antiplatelet therapeutic scheme. The CYP2C19*2 and CYP2C19*3 variants are loss-of-function alleles, leading to abolished CYP2C19 function and thus have the risk of thrombotic events for carriers of these alleles on standard dosages, while the CYP2C19*17 allele results in CYP2C19 hyperactivity. Aims: Here, we report our findings from a retrospective study to assess whether genotyping for the CYP2C19*2 allele was cost effective for myocardial infarction patients receiving clopidogrel treatment in the Serbian population compared with the nongenotype-guided treatment. Results: We found that 59.3% of the CYP2C19*1/*1 patients had a minor or major bleeding event versus 42.85% of the CYP2C19*1/*2 and *2/*2, while a reinfarction event occurred only in 2.3% of the CYP21C9*1/*1 patients, compared with 11.2% of the CYP2C19*1/*2 and CYP2C19*2/*2 patients. There were subtle differences between the two patient groups, as far as the duration of hospitalization and rehabilitation is concerned, in favor of the CYP2C19*1/*1 group. The mean cost for the CYP2C19*1/*1 patients was estimated at (sic)2547 versus (sic)2799 in the CYP2C19*1/*2 and CYP2C19*2/*2 patients. Furthermore, based on the overall CYP2C19*1/*2 genotype frequencies in the Serbian population, a break-even point analysis indicated that performing the genetic test prior to drug prescription represents a cost-saving option, saving (sic)13 per person on average. Conclusion: Overall, our data demonstrate that pharmacogenomics-guided clopidogrel treatment may represent a cost-saving approach for the management of myocardial infarction patients undergoing primary percutaneous coronary intervention in Serbia.",
publisher = "Future Medicine Ltd, London",
journal = "Pharmacogenomics",
title = "Economic analysis of pharmacogenomic-guided clopidogrel treatment in Serbian patients with myocardial infarction undergoing primary percutaneous coronary intervention",
pages = "1784-1775",
number = "16",
volume = "17",
doi = "10.2217/pgs-2016-0052"
}
Mitropoulou, C., Fragoulakis, V., Rakićević, L., Novković, M., Vozikis, A., Matić, D. M., Antonijević, N., Radojković, D., van Schaik, R. H.,& Patrinos, G. P.. (2016). Economic analysis of pharmacogenomic-guided clopidogrel treatment in Serbian patients with myocardial infarction undergoing primary percutaneous coronary intervention. in Pharmacogenomics
Future Medicine Ltd, London., 17(16), 1775-1784.
https://doi.org/10.2217/pgs-2016-0052
Mitropoulou C, Fragoulakis V, Rakićević L, Novković M, Vozikis A, Matić DM, Antonijević N, Radojković D, van Schaik RH, Patrinos GP. Economic analysis of pharmacogenomic-guided clopidogrel treatment in Serbian patients with myocardial infarction undergoing primary percutaneous coronary intervention. in Pharmacogenomics. 2016;17(16):1775-1784.
doi:10.2217/pgs-2016-0052 .
Mitropoulou, Christina, Fragoulakis, Vasilios, Rakićević, Ljiljana, Novković, Mirjana, Vozikis, Athanassios, Matić, Dragan M., Antonijević, Nebojša, Radojković, Dragica , van Schaik, Ron H., Patrinos, George P., "Economic analysis of pharmacogenomic-guided clopidogrel treatment in Serbian patients with myocardial infarction undergoing primary percutaneous coronary intervention" in Pharmacogenomics, 17, no. 16 (2016):1775-1784,
https://doi.org/10.2217/pgs-2016-0052 . .
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15
3
14

Differential expression and localization of Ankrd2 isoforms in human skeletal and cardiac muscles

Jasnić, Jovana; Krause, Sabine; Savić, Slobodan; Kojić, Ana; Kovcić, Vlado; Bošković, Srđan; Nestorović, Aleksandra; Rakićević, Ljiljana; Schreiber-Katz, Olivia; Vogel, Johannes G.; Schoser, Benedikt G.; Walter, Maggie C.; Valle, Giorgio; Radojković, Dragica; Faulkner, Georgine; Kojić, Snežana

(Springer, New York, 2016)

TY  - JOUR
AU  - Jasnić, Jovana
AU  - Krause, Sabine
AU  - Savić, Slobodan
AU  - Kojić, Ana
AU  - Kovcić, Vlado
AU  - Bošković, Srđan
AU  - Nestorović, Aleksandra
AU  - Rakićević, Ljiljana
AU  - Schreiber-Katz, Olivia
AU  - Vogel, Johannes G.
AU  - Schoser, Benedikt G.
AU  - Walter, Maggie C.
AU  - Valle, Giorgio
AU  - Radojković, Dragica
AU  - Faulkner, Georgine
AU  - Kojić, Snežana
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/933
AB  - Four human Ankrd2 transcripts, reported in the Ensembl database, code for distinct protein isoforms (360, 333, 327 and 300 aa), and so far, their existence, specific expression and localization patterns have not been studied in detail. Ankrd2 is preferentially expressed in the slow fibers of skeletal muscle. It is found in both the nuclei and the cytoplasm of skeletal muscle cells, and its localization is prone to change during differentiation and upon stress. Ankrd2 has also been detected in the heart, in ventricular cardiomyocytes and in the intercalated disks (ICDs). The main objective of this study was to distinguish between the Ankrd2 isoforms and to determine the contribution of each one to the general profile of Ankrd2 expression in striated muscles. We demonstrated that the known expression and localization pattern of Ankrd2 in striated muscle can be attributed to the isoform of 333 aa which is dominant in both tissues, while the designated cardiac and canonical isoform of 360 aa was less expressed in both tissues. The 360 aa isoform has a distinct nuclear localization in human skeletal muscle, as well as in primary myoblasts and myotubes. In contrast to the isoform of 333 aa, it was not preferentially expressed in slow fibers and not localized to the ICDs of human cardiomyocytes. Regulation of the expression of both isoforms is achieved at the transcriptional level. Our results set the stage for investigation of the specific functions and interactions of the Ankrd2 isoforms in healthy and diseased human striated muscles.
PB  - Springer, New York
T2  - Histochemistry and Cell Biology
T1  - Differential expression and localization of Ankrd2 isoforms in human skeletal and cardiac muscles
EP  - 584
IS  - 5
SP  - 569
VL  - 146
DO  - 10.1007/s00418-016-1465-0
ER  - 
@article{
author = "Jasnić, Jovana and Krause, Sabine and Savić, Slobodan and Kojić, Ana and Kovcić, Vlado and Bošković, Srđan and Nestorović, Aleksandra and Rakićević, Ljiljana and Schreiber-Katz, Olivia and Vogel, Johannes G. and Schoser, Benedikt G. and Walter, Maggie C. and Valle, Giorgio and Radojković, Dragica and Faulkner, Georgine and Kojić, Snežana",
year = "2016",
abstract = "Four human Ankrd2 transcripts, reported in the Ensembl database, code for distinct protein isoforms (360, 333, 327 and 300 aa), and so far, their existence, specific expression and localization patterns have not been studied in detail. Ankrd2 is preferentially expressed in the slow fibers of skeletal muscle. It is found in both the nuclei and the cytoplasm of skeletal muscle cells, and its localization is prone to change during differentiation and upon stress. Ankrd2 has also been detected in the heart, in ventricular cardiomyocytes and in the intercalated disks (ICDs). The main objective of this study was to distinguish between the Ankrd2 isoforms and to determine the contribution of each one to the general profile of Ankrd2 expression in striated muscles. We demonstrated that the known expression and localization pattern of Ankrd2 in striated muscle can be attributed to the isoform of 333 aa which is dominant in both tissues, while the designated cardiac and canonical isoform of 360 aa was less expressed in both tissues. The 360 aa isoform has a distinct nuclear localization in human skeletal muscle, as well as in primary myoblasts and myotubes. In contrast to the isoform of 333 aa, it was not preferentially expressed in slow fibers and not localized to the ICDs of human cardiomyocytes. Regulation of the expression of both isoforms is achieved at the transcriptional level. Our results set the stage for investigation of the specific functions and interactions of the Ankrd2 isoforms in healthy and diseased human striated muscles.",
publisher = "Springer, New York",
journal = "Histochemistry and Cell Biology",
title = "Differential expression and localization of Ankrd2 isoforms in human skeletal and cardiac muscles",
pages = "584-569",
number = "5",
volume = "146",
doi = "10.1007/s00418-016-1465-0"
}
Jasnić, J., Krause, S., Savić, S., Kojić, A., Kovcić, V., Bošković, S., Nestorović, A., Rakićević, L., Schreiber-Katz, O., Vogel, J. G., Schoser, B. G., Walter, M. C., Valle, G., Radojković, D., Faulkner, G.,& Kojić, S.. (2016). Differential expression and localization of Ankrd2 isoforms in human skeletal and cardiac muscles. in Histochemistry and Cell Biology
Springer, New York., 146(5), 569-584.
https://doi.org/10.1007/s00418-016-1465-0
Jasnić J, Krause S, Savić S, Kojić A, Kovcić V, Bošković S, Nestorović A, Rakićević L, Schreiber-Katz O, Vogel JG, Schoser BG, Walter MC, Valle G, Radojković D, Faulkner G, Kojić S. Differential expression and localization of Ankrd2 isoforms in human skeletal and cardiac muscles. in Histochemistry and Cell Biology. 2016;146(5):569-584.
doi:10.1007/s00418-016-1465-0 .
Jasnić, Jovana, Krause, Sabine, Savić, Slobodan, Kojić, Ana, Kovcić, Vlado, Bošković, Srđan, Nestorović, Aleksandra, Rakićević, Ljiljana, Schreiber-Katz, Olivia, Vogel, Johannes G., Schoser, Benedikt G., Walter, Maggie C., Valle, Giorgio, Radojković, Dragica, Faulkner, Georgine, Kojić, Snežana, "Differential expression and localization of Ankrd2 isoforms in human skeletal and cardiac muscles" in Histochemistry and Cell Biology, 146, no. 5 (2016):569-584,
https://doi.org/10.1007/s00418-016-1465-0 . .
2
6
1
6

Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije

Bačković, Dragana; Ignjatović, Svetlana; Rakićević, Ljiljana; Kušić-Tišma, Jelena; Radojković, Dragica; Ćalija, Branko; Strugarević, Evgenija; Radak, Đorđe; Kovač, Mirjana

(Društvo medicinskih biohemičara Srbije, Beograd i Versita, 2016)

TY  - JOUR
AU  - Bačković, Dragana
AU  - Ignjatović, Svetlana
AU  - Rakićević, Ljiljana
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica
AU  - Ćalija, Branko
AU  - Strugarević, Evgenija
AU  - Radak, Đorđe
AU  - Kovač, Mirjana
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/988
AB  - Uvod: I pored dokazanog kliničkog efekta oralne antiagregacijske terapije, značajan broj pacijenata nema adekvatan odgovor na primenjeni klopidogrel. Cilj naše studije je bio da se utvrdi uticaj prisutne CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod pacijenata sa stenozom karotidne arterije. Metode: U jednogodišnju prospektivnu studiju uključeno je 112 pacijenata sa stenozom karotidne arterije kod kojih je izvršena endarterektomija. Posle operativnog zahvata, pacijenti su primali 75 mg dnevno klopidogrela u trajanju od najmanje mesec dana. Svi ispitanici su praćeni od momenta prijema. Za CYP2C19 genotipizaciju korišćen je TaqMan test. Uticaj CYP2C19*2 alela na trombocitnu reaktivnost ispitivan je primenom multiple-electrode aggregometry (MEA). Rezultati: Rezultati genotipizacije su pokazali da su 82 (73,2%) ispitanika homozigoti za wild-type, 29 (25,9%) heterozigoti za CYP2C19*2 alel, dok je 1 (0,9%) bio homozigot za CYP2C19*2. Nakon 24 sata, u grupi sa wild-type genotipom 29,3% ispitanika dali su odgovor na klopidogrel, a u grupi sa CYP2C19*2 varijantom gena 10% ispitanika. U grupi sa wild-type genotipom, 74,4% ispitanika su imali terapijski odgovor nakon 7 dana, odnosno 82,9% nakon 30 dana od primene klopidogrela. U grupi sa CYP2C19*2 alelom broj ispitanika sa terapijskim odgovorom raste do 46,7% nakon 7 dana, odnosno do 53,3% nakon 30 dana od primene klopidogrela. Rizik za slab odgovor je veći kod nosilaca CYP2C19*2 alela u odnosu na nenosioce (wild-type) (OR 4,250, 95% CI 1 .695 -10.658 , P lt  0,01). Zaključak: CYP2C19*2 varijanta gena značajno utiče na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije kod kojih je izvršena endarterektomija.
AB  - Background: Despite the proven clinical effect of oral antiplatelet drugs, a considerable number of patients do not have an adequate response to clopidogrel. The aim of our study was to determine the influence of CYP2C19*2 loss-of-function variant allele on clopidogrel responsiveness in patients with carotid artery stenosis. Methods: One hundred and twelve patients with carotid artery stenosis undergoing endarterectomy were included in this one-year prospective study. All of them received clopidogrel (75 mg daily) for at least 30 days after the intervention. They were followed from the moment of hospital admission. CYP2C19*2 genotyping was performed by TaqMan Assay. The influence of c Yp 2C 19*2 variant allele on clopidogrel platelet reactivity was determined using multiple-electrode aggregometry (MEA). Results: Genotyping results showed that 82 (73.2% ) patients were homozygous for wild type, 29 (25.9%) were heterozygous for the CYP2C19*2 allele and 1 (0.9%) was CYP2C19*2 homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with the CYP2C19*2 alleles 10%. In the wild type group, 74.4% were clopidogrel responders after 7 days of taking the drug; 82.9% after 30 days of clopidogrel introduction, respectively. In patients with the CYP2C19*2 alleles the number of responders increased up to 46.7% after 7 days; 53.3% after 30 days of taking the drug, respectively. The risk for being a low-responder is higher for the patients heterozygous for the c Yp 2C 19*2 allele vs. wildtype (OR 4.250, 95% CI 1.695 -10.658 , P lt  0.01). Conclusions: The CYP2C19*2 loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije
T1  - Influence of CYP2C19*2 gene variant on therapeutic response during clopidogrel treatment in patients with carotid artery stenosis
EP  - 33
IS  - 1
SP  - 26
VL  - 35
DO  - 10.1515/jomb-2015-0009
ER  - 
@article{
author = "Bačković, Dragana and Ignjatović, Svetlana and Rakićević, Ljiljana and Kušić-Tišma, Jelena and Radojković, Dragica and Ćalija, Branko and Strugarević, Evgenija and Radak, Đorđe and Kovač, Mirjana",
year = "2016",
abstract = "Uvod: I pored dokazanog kliničkog efekta oralne antiagregacijske terapije, značajan broj pacijenata nema adekvatan odgovor na primenjeni klopidogrel. Cilj naše studije je bio da se utvrdi uticaj prisutne CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod pacijenata sa stenozom karotidne arterije. Metode: U jednogodišnju prospektivnu studiju uključeno je 112 pacijenata sa stenozom karotidne arterije kod kojih je izvršena endarterektomija. Posle operativnog zahvata, pacijenti su primali 75 mg dnevno klopidogrela u trajanju od najmanje mesec dana. Svi ispitanici su praćeni od momenta prijema. Za CYP2C19 genotipizaciju korišćen je TaqMan test. Uticaj CYP2C19*2 alela na trombocitnu reaktivnost ispitivan je primenom multiple-electrode aggregometry (MEA). Rezultati: Rezultati genotipizacije su pokazali da su 82 (73,2%) ispitanika homozigoti za wild-type, 29 (25,9%) heterozigoti za CYP2C19*2 alel, dok je 1 (0,9%) bio homozigot za CYP2C19*2. Nakon 24 sata, u grupi sa wild-type genotipom 29,3% ispitanika dali su odgovor na klopidogrel, a u grupi sa CYP2C19*2 varijantom gena 10% ispitanika. U grupi sa wild-type genotipom, 74,4% ispitanika su imali terapijski odgovor nakon 7 dana, odnosno 82,9% nakon 30 dana od primene klopidogrela. U grupi sa CYP2C19*2 alelom broj ispitanika sa terapijskim odgovorom raste do 46,7% nakon 7 dana, odnosno do 53,3% nakon 30 dana od primene klopidogrela. Rizik za slab odgovor je veći kod nosilaca CYP2C19*2 alela u odnosu na nenosioce (wild-type) (OR 4,250, 95% CI 1 .695 -10.658 , P lt  0,01). Zaključak: CYP2C19*2 varijanta gena značajno utiče na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije kod kojih je izvršena endarterektomija., Background: Despite the proven clinical effect of oral antiplatelet drugs, a considerable number of patients do not have an adequate response to clopidogrel. The aim of our study was to determine the influence of CYP2C19*2 loss-of-function variant allele on clopidogrel responsiveness in patients with carotid artery stenosis. Methods: One hundred and twelve patients with carotid artery stenosis undergoing endarterectomy were included in this one-year prospective study. All of them received clopidogrel (75 mg daily) for at least 30 days after the intervention. They were followed from the moment of hospital admission. CYP2C19*2 genotyping was performed by TaqMan Assay. The influence of c Yp 2C 19*2 variant allele on clopidogrel platelet reactivity was determined using multiple-electrode aggregometry (MEA). Results: Genotyping results showed that 82 (73.2% ) patients were homozygous for wild type, 29 (25.9%) were heterozygous for the CYP2C19*2 allele and 1 (0.9%) was CYP2C19*2 homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with the CYP2C19*2 alleles 10%. In the wild type group, 74.4% were clopidogrel responders after 7 days of taking the drug; 82.9% after 30 days of clopidogrel introduction, respectively. In patients with the CYP2C19*2 alleles the number of responders increased up to 46.7% after 7 days; 53.3% after 30 days of taking the drug, respectively. The risk for being a low-responder is higher for the patients heterozygous for the c Yp 2C 19*2 allele vs. wildtype (OR 4.250, 95% CI 1.695 -10.658 , P lt  0.01). Conclusions: The CYP2C19*2 loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije, Influence of CYP2C19*2 gene variant on therapeutic response during clopidogrel treatment in patients with carotid artery stenosis",
pages = "33-26",
number = "1",
volume = "35",
doi = "10.1515/jomb-2015-0009"
}
Bačković, D., Ignjatović, S., Rakićević, L., Kušić-Tišma, J., Radojković, D., Ćalija, B., Strugarević, E., Radak, Đ.,& Kovač, M.. (2016). Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 35(1), 26-33.
https://doi.org/10.1515/jomb-2015-0009
Bačković D, Ignjatović S, Rakićević L, Kušić-Tišma J, Radojković D, Ćalija B, Strugarević E, Radak Đ, Kovač M. Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije. in Journal of Medical Biochemistry. 2016;35(1):26-33.
doi:10.1515/jomb-2015-0009 .
Bačković, Dragana, Ignjatović, Svetlana, Rakićević, Ljiljana, Kušić-Tišma, Jelena, Radojković, Dragica, Ćalija, Branko, Strugarević, Evgenija, Radak, Đorđe, Kovač, Mirjana, "Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije" in Journal of Medical Biochemistry, 35, no. 1 (2016):26-33,
https://doi.org/10.1515/jomb-2015-0009 . .
3
3

Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study

Backović, Dragana; Ignjatović, Svetlana; Rakićević, Ljiljana; Novković, Mirjana; Kušić-Tišma, Jelena; Radojković, Dragica; Strugarević, Evgenija; Calija, Branko; Radak, Djordje; Kovač, Mirjana

(Bentham Science Publ Ltd, Sharjah, 2016)

TY  - JOUR
AU  - Backović, Dragana
AU  - Ignjatović, Svetlana
AU  - Rakićević, Ljiljana
AU  - Novković, Mirjana
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica
AU  - Strugarević, Evgenija
AU  - Calija, Branko
AU  - Radak, Djordje
AU  - Kovač, Mirjana
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/920
AB  - Objectives: A considerable number of patients do not achieve an adequate response to clopidogrel. Our study aimed to evaluate genetic and non-genetic factors as possible risks for clopidogrel high on-treatment platelet reactivity (HTPR) in patients (n=112) with carotid artery stenosis undergoing endarterectomy (CEA). Methods: Using multiple-electrode impedance aggregometry (MEA) the antiplatelet effectiveness of clopidogrel was measured after 24 h, 7 and 30 days of clopidogrel treatment, which was introduced after elective CEA at a dose of 75 mg daily, for at least 30 days. Results: HTPR was observed among 25% patients after clopidogrel therapy for 30 days. Further analysis showed that 53.3% of patients carrying the CYP2C19*2 gene variant had clopidogrel-HTPR, while in the wild type group there were 14.6% (p lt 0.001). Multivariate logistic regression analysis identified the CYP2C19*2 variant allele (OR 4.384; 95% CI 1.296-14.833, p=0.017) and high total cholesterol level (OR 2.090; 95% CI 1.263-3.459, p=0.004) as the only independent risk factors for clopidogrel-HTPR. Conclusion: The CYP2C19*2 gene variant and high total cholesterol level were major factors for clopidogrel-HTPR in patients with carotid artery stenosis undergoing CEA.
PB  - Bentham Science Publ Ltd, Sharjah
T2  - Current Vascular Pharmacology
T1  - Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study
EP  - 569
IS  - 6
SP  - 563
VL  - 14
DO  - 10.2174/1570161114666160714103148
ER  - 
@article{
author = "Backović, Dragana and Ignjatović, Svetlana and Rakićević, Ljiljana and Novković, Mirjana and Kušić-Tišma, Jelena and Radojković, Dragica and Strugarević, Evgenija and Calija, Branko and Radak, Djordje and Kovač, Mirjana",
year = "2016",
abstract = "Objectives: A considerable number of patients do not achieve an adequate response to clopidogrel. Our study aimed to evaluate genetic and non-genetic factors as possible risks for clopidogrel high on-treatment platelet reactivity (HTPR) in patients (n=112) with carotid artery stenosis undergoing endarterectomy (CEA). Methods: Using multiple-electrode impedance aggregometry (MEA) the antiplatelet effectiveness of clopidogrel was measured after 24 h, 7 and 30 days of clopidogrel treatment, which was introduced after elective CEA at a dose of 75 mg daily, for at least 30 days. Results: HTPR was observed among 25% patients after clopidogrel therapy for 30 days. Further analysis showed that 53.3% of patients carrying the CYP2C19*2 gene variant had clopidogrel-HTPR, while in the wild type group there were 14.6% (p lt 0.001). Multivariate logistic regression analysis identified the CYP2C19*2 variant allele (OR 4.384; 95% CI 1.296-14.833, p=0.017) and high total cholesterol level (OR 2.090; 95% CI 1.263-3.459, p=0.004) as the only independent risk factors for clopidogrel-HTPR. Conclusion: The CYP2C19*2 gene variant and high total cholesterol level were major factors for clopidogrel-HTPR in patients with carotid artery stenosis undergoing CEA.",
publisher = "Bentham Science Publ Ltd, Sharjah",
journal = "Current Vascular Pharmacology",
title = "Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study",
pages = "569-563",
number = "6",
volume = "14",
doi = "10.2174/1570161114666160714103148"
}
Backović, D., Ignjatović, S., Rakićević, L., Novković, M., Kušić-Tišma, J., Radojković, D., Strugarević, E., Calija, B., Radak, D.,& Kovač, M.. (2016). Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study. in Current Vascular Pharmacology
Bentham Science Publ Ltd, Sharjah., 14(6), 563-569.
https://doi.org/10.2174/1570161114666160714103148
Backović D, Ignjatović S, Rakićević L, Novković M, Kušić-Tišma J, Radojković D, Strugarević E, Calija B, Radak D, Kovač M. Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study. in Current Vascular Pharmacology. 2016;14(6):563-569.
doi:10.2174/1570161114666160714103148 .
Backović, Dragana, Ignjatović, Svetlana, Rakićević, Ljiljana, Novković, Mirjana, Kušić-Tišma, Jelena, Radojković, Dragica, Strugarević, Evgenija, Calija, Branko, Radak, Djordje, Kovač, Mirjana, "Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study" in Current Vascular Pharmacology, 14, no. 6 (2016):563-569,
https://doi.org/10.2174/1570161114666160714103148 . .
5
3
5

Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy

Backović, D.; Ignjatović, S.; Rakićević, Ljiljana; Novković, Mirjana; Kušić-Tišma, Jelena; Radojković, Dragica; Strugarević, E.; Calija, B.; Radak, D.; Kovač, Mirjana

(Wiley-Blackwell, Hoboken, 2016)

TY  - CONF
AU  - Backović, D.
AU  - Ignjatović, S.
AU  - Rakićević, Ljiljana
AU  - Novković, Mirjana
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica
AU  - Strugarević, E.
AU  - Calija, B.
AU  - Radak, D.
AU  - Kovač, Mirjana
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/940
PB  - Wiley-Blackwell, Hoboken
C3  - Journal of Thrombosis and Haemostasis
T1  - Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy
EP  - 110
SP  - 110
VL  - 14
UR  - https://hdl.handle.net/21.15107/rcub_imagine_940
ER  - 
@conference{
author = "Backović, D. and Ignjatović, S. and Rakićević, Ljiljana and Novković, Mirjana and Kušić-Tišma, Jelena and Radojković, Dragica and Strugarević, E. and Calija, B. and Radak, D. and Kovač, Mirjana",
year = "2016",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Journal of Thrombosis and Haemostasis",
title = "Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy",
pages = "110-110",
volume = "14",
url = "https://hdl.handle.net/21.15107/rcub_imagine_940"
}
Backović, D., Ignjatović, S., Rakićević, L., Novković, M., Kušić-Tišma, J., Radojković, D., Strugarević, E., Calija, B., Radak, D.,& Kovač, M.. (2016). Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy. in Journal of Thrombosis and Haemostasis
Wiley-Blackwell, Hoboken., 14, 110-110.
https://hdl.handle.net/21.15107/rcub_imagine_940
Backović D, Ignjatović S, Rakićević L, Novković M, Kušić-Tišma J, Radojković D, Strugarević E, Calija B, Radak D, Kovač M. Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy. in Journal of Thrombosis and Haemostasis. 2016;14:110-110.
https://hdl.handle.net/21.15107/rcub_imagine_940 .
Backović, D., Ignjatović, S., Rakićević, Ljiljana, Novković, Mirjana, Kušić-Tišma, Jelena, Radojković, Dragica, Strugarević, E., Calija, B., Radak, D., Kovač, Mirjana, "Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy" in Journal of Thrombosis and Haemostasis, 14 (2016):110-110,
https://hdl.handle.net/21.15107/rcub_imagine_940 .

Cardiac transcription factor Nkx2.5 interacts with p53 and modulates its activity

Kojić, Snežana; Nestorović, Aleksandra; Rakićević, Ljiljana; Protić, Olga; Jasnić, Jovana; Faulkner, Georgine; Radojković, Dragica

(Elsevier Science Inc, New York, 2015)

TY  - JOUR
AU  - Kojić, Snežana
AU  - Nestorović, Aleksandra
AU  - Rakićević, Ljiljana
AU  - Protić, Olga
AU  - Jasnić, Jovana
AU  - Faulkner, Georgine
AU  - Radojković, Dragica
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/879
AB  - Transcription factor Nkx2.5, essential for heart development, regulates cardiomyocyte-specific gene expression through combinatorial interactions with other cardiac-restricted (GATA4 and dHAND) or ubiquitous (p300) transcription regulators. Here we demonstrate that Nkx2.5 and p53 synergistically activate the promoter of the striated muscle stress responsive transcriptional cofactor Ankrd2, involved in coordination of proliferation and apoptosis during myogenic differentiation. Moreover, the p53 protein is able to interact with both wild type Nkx2.5 and its mutant Delta Nkx2.5 (aa 1-198) found in patients with diverse cardiac malformations. Nkx2.5 interaction site of p53 maps to the C terminal region, while p53 binding site on Nkx2.5 lies outside its C terminus. In addition, overexpression of Nkx2.5 has a modulatory, promoter dependent effect on p53 transactivation, while the mutant significantly abolished p53 activity on the Mdm2, p21(WAF1/CIP1) and Box promoters. Their physical interaction contributes to the observed behavior in the case of the Mdm2 promoter. Our data provide a new evidence for the role of p53 in cardiac function through interaction with Nkx2.5.
PB  - Elsevier Science Inc, New York
T2  - Archives of Biochemistry and Biophysics
T1  - Cardiac transcription factor Nkx2.5 interacts with p53 and modulates its activity
EP  - 53
SP  - 45
VL  - 569
DO  - 10.1016/j.abb.2015.02.001
ER  - 
@article{
author = "Kojić, Snežana and Nestorović, Aleksandra and Rakićević, Ljiljana and Protić, Olga and Jasnić, Jovana and Faulkner, Georgine and Radojković, Dragica",
year = "2015",
abstract = "Transcription factor Nkx2.5, essential for heart development, regulates cardiomyocyte-specific gene expression through combinatorial interactions with other cardiac-restricted (GATA4 and dHAND) or ubiquitous (p300) transcription regulators. Here we demonstrate that Nkx2.5 and p53 synergistically activate the promoter of the striated muscle stress responsive transcriptional cofactor Ankrd2, involved in coordination of proliferation and apoptosis during myogenic differentiation. Moreover, the p53 protein is able to interact with both wild type Nkx2.5 and its mutant Delta Nkx2.5 (aa 1-198) found in patients with diverse cardiac malformations. Nkx2.5 interaction site of p53 maps to the C terminal region, while p53 binding site on Nkx2.5 lies outside its C terminus. In addition, overexpression of Nkx2.5 has a modulatory, promoter dependent effect on p53 transactivation, while the mutant significantly abolished p53 activity on the Mdm2, p21(WAF1/CIP1) and Box promoters. Their physical interaction contributes to the observed behavior in the case of the Mdm2 promoter. Our data provide a new evidence for the role of p53 in cardiac function through interaction with Nkx2.5.",
publisher = "Elsevier Science Inc, New York",
journal = "Archives of Biochemistry and Biophysics",
title = "Cardiac transcription factor Nkx2.5 interacts with p53 and modulates its activity",
pages = "53-45",
volume = "569",
doi = "10.1016/j.abb.2015.02.001"
}
Kojić, S., Nestorović, A., Rakićević, L., Protić, O., Jasnić, J., Faulkner, G.,& Radojković, D.. (2015). Cardiac transcription factor Nkx2.5 interacts with p53 and modulates its activity. in Archives of Biochemistry and Biophysics
Elsevier Science Inc, New York., 569, 45-53.
https://doi.org/10.1016/j.abb.2015.02.001
Kojić S, Nestorović A, Rakićević L, Protić O, Jasnić J, Faulkner G, Radojković D. Cardiac transcription factor Nkx2.5 interacts with p53 and modulates its activity. in Archives of Biochemistry and Biophysics. 2015;569:45-53.
doi:10.1016/j.abb.2015.02.001 .
Kojić, Snežana, Nestorović, Aleksandra, Rakićević, Ljiljana, Protić, Olga, Jasnić, Jovana, Faulkner, Georgine, Radojković, Dragica, "Cardiac transcription factor Nkx2.5 interacts with p53 and modulates its activity" in Archives of Biochemistry and Biophysics, 569 (2015):45-53,
https://doi.org/10.1016/j.abb.2015.02.001 . .
3
8
3
10

Does Anticoagulant Therapy Improve Pregnancy Outcome Equally, Regardless of Specific Thrombophilia Type?

Kovač, Mirjana; Miković, Zeljko; Mitić, Gorana; Đorđević, Valentina; Mandić, Vesna; Rakićević, Ljiljana; Radojković, Dragica

(Sage Publications Inc, Thousand Oaks, 2014)

TY  - JOUR
AU  - Kovač, Mirjana
AU  - Miković, Zeljko
AU  - Mitić, Gorana
AU  - Đorđević, Valentina
AU  - Mandić, Vesna
AU  - Rakićević, Ljiljana
AU  - Radojković, Dragica
PY  - 2014
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/783
AB  - The study was conducted to evaluate the effect of anticoagulant therapy in women with thrombophilia and to detect the possible differences among carriers of mutations (factor V [FV] Leiden and FIIG20210) and those with natural anticoagulant deficiency. The 4-year prospective investigation included 85 pregnant women, with a history of recurrent fetal loss (RFL). They were treated with prophylactic doses of low-molecular-weight heparin (nadroparin) starting from 6 to 8 weeks of gestation. Pregnancy outcomes were evaluated based on the thrombophilia type. Carriers of thrombophilic mutations had a live birth rate of 93%, compared to 41.6% for women with natural anticoagulant deficiencies. Significant differences between the groups were also observed for intrauterine fetal death, intrauterine growth restriction, and postpartum thrombosis. The optimal therapy for women with natural anticoagulant deficiency and RFL remains unclear and future prospective study with a large number of patients is required to determine the best treatment for these severe thrombophilic conditions.
PB  - Sage Publications Inc, Thousand Oaks
T2  - Clinical and Applied Thrombosis-Hemostasis
T1  - Does Anticoagulant Therapy Improve Pregnancy Outcome Equally, Regardless of Specific Thrombophilia Type?
EP  - 189
IS  - 2
SP  - 184
VL  - 20
DO  - 10.1177/1076029612468940
ER  - 
@article{
author = "Kovač, Mirjana and Miković, Zeljko and Mitić, Gorana and Đorđević, Valentina and Mandić, Vesna and Rakićević, Ljiljana and Radojković, Dragica",
year = "2014",
abstract = "The study was conducted to evaluate the effect of anticoagulant therapy in women with thrombophilia and to detect the possible differences among carriers of mutations (factor V [FV] Leiden and FIIG20210) and those with natural anticoagulant deficiency. The 4-year prospective investigation included 85 pregnant women, with a history of recurrent fetal loss (RFL). They were treated with prophylactic doses of low-molecular-weight heparin (nadroparin) starting from 6 to 8 weeks of gestation. Pregnancy outcomes were evaluated based on the thrombophilia type. Carriers of thrombophilic mutations had a live birth rate of 93%, compared to 41.6% for women with natural anticoagulant deficiencies. Significant differences between the groups were also observed for intrauterine fetal death, intrauterine growth restriction, and postpartum thrombosis. The optimal therapy for women with natural anticoagulant deficiency and RFL remains unclear and future prospective study with a large number of patients is required to determine the best treatment for these severe thrombophilic conditions.",
publisher = "Sage Publications Inc, Thousand Oaks",
journal = "Clinical and Applied Thrombosis-Hemostasis",
title = "Does Anticoagulant Therapy Improve Pregnancy Outcome Equally, Regardless of Specific Thrombophilia Type?",
pages = "189-184",
number = "2",
volume = "20",
doi = "10.1177/1076029612468940"
}
Kovač, M., Miković, Z., Mitić, G., Đorđević, V., Mandić, V., Rakićević, L.,& Radojković, D.. (2014). Does Anticoagulant Therapy Improve Pregnancy Outcome Equally, Regardless of Specific Thrombophilia Type?. in Clinical and Applied Thrombosis-Hemostasis
Sage Publications Inc, Thousand Oaks., 20(2), 184-189.
https://doi.org/10.1177/1076029612468940
Kovač M, Miković Z, Mitić G, Đorđević V, Mandić V, Rakićević L, Radojković D. Does Anticoagulant Therapy Improve Pregnancy Outcome Equally, Regardless of Specific Thrombophilia Type?. in Clinical and Applied Thrombosis-Hemostasis. 2014;20(2):184-189.
doi:10.1177/1076029612468940 .
Kovač, Mirjana, Miković, Zeljko, Mitić, Gorana, Đorđević, Valentina, Mandić, Vesna, Rakićević, Ljiljana, Radojković, Dragica, "Does Anticoagulant Therapy Improve Pregnancy Outcome Equally, Regardless of Specific Thrombophilia Type?" in Clinical and Applied Thrombosis-Hemostasis, 20, no. 2 (2014):184-189,
https://doi.org/10.1177/1076029612468940 . .
7
3
6

Risk factors for thrombosis in Serbian children

Serbić-Nonković, Olivera M.; Kuzmanović, Milos B.; Rakićević, Ljiljana; Đorđević, Valentina; Veljković, Dobrila K.; Prijić, Sergej M.; Kovacević, Gordana S.; Rakonjac, Zorica M.; Kosutić, Jovan Lj; Vujić, Dragana S.; Micić, Dragan V.; Janković, Borisav Z.; Radojković, Dragica

(Lippincott Williams & Wilkins, Philadelphia, 2014)

TY  - JOUR
AU  - Serbić-Nonković, Olivera M.
AU  - Kuzmanović, Milos B.
AU  - Rakićević, Ljiljana
AU  - Đorđević, Valentina
AU  - Veljković, Dobrila K.
AU  - Prijić, Sergej M.
AU  - Kovacević, Gordana S.
AU  - Rakonjac, Zorica M.
AU  - Kosutić, Jovan Lj
AU  - Vujić, Dragana S.
AU  - Micić, Dragan V.
AU  - Janković, Borisav Z.
AU  - Radojković, Dragica
PY  - 2014
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/772
AB  - Venous and arterial thromboses are increasingly encountered in the pediatric population. We present results of a case-control study of inherited and acquired risk factors for thrombosis in 129 pediatric patients from the first day of life to 18 years. The aims of study were to determine the importance of thrombophilic risk factors and comorbidity as a cause of thrombosis in children. Single thrombophilic risk factor was found in 24.4% (n=21), whereas combined thrombophilic factors were found in 15.1% (n=13) patients. A total of 87.2% of the children had recognized thrombophilic risk factors for thrombosis and/or additional comorbid risk factors. The single independent risk factors for thrombosis were mutation of factor V Leiden (P=0.021), lupus anticoagulant antibodies (P=0.028), and comorbidity (P=0.000). Mutation of factor V Leiden [odds ratio (OR), 6.2 (95% confidence interval, CI 1.1-38.1, P=0.048] was found to be a risk factor for venous thrombosis. Lupus anticoagulant antibodies were related to both venous (P=0.008) and arterial thrombosis (P=0.016). The frequency of inherited thrombophilic factors were the same in neonates and adolescents (23%). The prothrombotic gene mutations were present in 18.6% (n=8) of asymptomatic children. Our study confirms that thrombosis in children is a multifactorial disorder, and associated most with the underlying medical disease (comorbidity) for vein thrombosis [OR, 18.6 (95% CI 3.7-93.4), P=0.000] and for arterial thrombosis [OR, 10.5 (95% CI 2.2-49.9) P=0.003]. Inherited thrombophilic disorders contributed to the development of thrombosis in children.
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Blood Coagulation & Fibrinolysis
T1  - Risk factors for thrombosis in Serbian children
EP  - 32
IS  - 1
SP  - 25
VL  - 25
DO  - 10.1097/MBC.0b013e328364c217
ER  - 
@article{
author = "Serbić-Nonković, Olivera M. and Kuzmanović, Milos B. and Rakićević, Ljiljana and Đorđević, Valentina and Veljković, Dobrila K. and Prijić, Sergej M. and Kovacević, Gordana S. and Rakonjac, Zorica M. and Kosutić, Jovan Lj and Vujić, Dragana S. and Micić, Dragan V. and Janković, Borisav Z. and Radojković, Dragica",
year = "2014",
abstract = "Venous and arterial thromboses are increasingly encountered in the pediatric population. We present results of a case-control study of inherited and acquired risk factors for thrombosis in 129 pediatric patients from the first day of life to 18 years. The aims of study were to determine the importance of thrombophilic risk factors and comorbidity as a cause of thrombosis in children. Single thrombophilic risk factor was found in 24.4% (n=21), whereas combined thrombophilic factors were found in 15.1% (n=13) patients. A total of 87.2% of the children had recognized thrombophilic risk factors for thrombosis and/or additional comorbid risk factors. The single independent risk factors for thrombosis were mutation of factor V Leiden (P=0.021), lupus anticoagulant antibodies (P=0.028), and comorbidity (P=0.000). Mutation of factor V Leiden [odds ratio (OR), 6.2 (95% confidence interval, CI 1.1-38.1, P=0.048] was found to be a risk factor for venous thrombosis. Lupus anticoagulant antibodies were related to both venous (P=0.008) and arterial thrombosis (P=0.016). The frequency of inherited thrombophilic factors were the same in neonates and adolescents (23%). The prothrombotic gene mutations were present in 18.6% (n=8) of asymptomatic children. Our study confirms that thrombosis in children is a multifactorial disorder, and associated most with the underlying medical disease (comorbidity) for vein thrombosis [OR, 18.6 (95% CI 3.7-93.4), P=0.000] and for arterial thrombosis [OR, 10.5 (95% CI 2.2-49.9) P=0.003]. Inherited thrombophilic disorders contributed to the development of thrombosis in children.",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Blood Coagulation & Fibrinolysis",
title = "Risk factors for thrombosis in Serbian children",
pages = "32-25",
number = "1",
volume = "25",
doi = "10.1097/MBC.0b013e328364c217"
}
Serbić-Nonković, O. M., Kuzmanović, M. B., Rakićević, L., Đorđević, V., Veljković, D. K., Prijić, S. M., Kovacević, G. S., Rakonjac, Z. M., Kosutić, J. L., Vujić, D. S., Micić, D. V., Janković, B. Z.,& Radojković, D.. (2014). Risk factors for thrombosis in Serbian children. in Blood Coagulation & Fibrinolysis
Lippincott Williams & Wilkins, Philadelphia., 25(1), 25-32.
https://doi.org/10.1097/MBC.0b013e328364c217
Serbić-Nonković OM, Kuzmanović MB, Rakićević L, Đorđević V, Veljković DK, Prijić SM, Kovacević GS, Rakonjac ZM, Kosutić JL, Vujić DS, Micić DV, Janković BZ, Radojković D. Risk factors for thrombosis in Serbian children. in Blood Coagulation & Fibrinolysis. 2014;25(1):25-32.
doi:10.1097/MBC.0b013e328364c217 .
Serbić-Nonković, Olivera M., Kuzmanović, Milos B., Rakićević, Ljiljana, Đorđević, Valentina, Veljković, Dobrila K., Prijić, Sergej M., Kovacević, Gordana S., Rakonjac, Zorica M., Kosutić, Jovan Lj, Vujić, Dragana S., Micić, Dragan V., Janković, Borisav Z., Radojković, Dragica, "Risk factors for thrombosis in Serbian children" in Blood Coagulation & Fibrinolysis, 25, no. 1 (2014):25-32,
https://doi.org/10.1097/MBC.0b013e328364c217 . .
2
1
2

Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation

Kovač, Mirjana; Rakićević, Ljiljana; Kušić-Tišma, Jelena; Radojković, Dragica

(Springer, Dordrecht, 2013)

TY  - JOUR
AU  - Kovač, Mirjana
AU  - Rakićević, Ljiljana
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/679
AB  - Several studies have linked mutations in the genes encoding cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1) to a reduced VKA dose requirement and an increased risk of bleeding. Nevertheless, implementation of genotyping as a routine practice is still controversial. Our study was conducted in order to investigate the impact of genetic factors, presence of VKORC1-c.1639A, CYP2C*2 and CYP2C*3 among outpatients referred to Anticoagulation Service due to extremely unstable anticoagulant therapy. From 2008 to 2011, 68 patients, mean age 65.9, were included in the study. They were referred from primary care physicians due to inability to sustain the therapeutic range in the period of initiation of anticoagulant therapy. Genotyping results showed that 17 (25 %) of them were carriers of both CYP2C9 and VKORC1 variant alleles, 38 (55.9 %) were carriers of VKORC1 c.1639AA, 6 (8.8 %) were carriers of CYP2C9 variant alleles, while 7 (10.3 %) of them were carriers of wild type alleles. INR control upon admission showed that 34 (50 %) of them were over-anticoagulated, while 12 (17.6 %) of them had subsequent bleeding complications. Among over-anticoagulated patients, 32 were carriers of mutated alleles in both CYP2C9 and VKORC1 gene or VKORC1 alone, while 2 of patients carried wild type alleles. In addition to presence of CYP2C9 or VKORC 1 alleles, older age was an important factor related to a lower dose and risk for over-anticoagulation. Genotype (CYP2C9/VKORC1) and age are the most important factors that could predispose an extreme response and subsequent bleeding complications during the initiation of VKA.
PB  - Springer, Dordrecht
T2  - Journal of Thrombosis and Thrombolysis
T1  - Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation
EP  - 94
IS  - 1
SP  - 90
VL  - 35
DO  - 10.1007/s11239-012-0769-8
ER  - 
@article{
author = "Kovač, Mirjana and Rakićević, Ljiljana and Kušić-Tišma, Jelena and Radojković, Dragica",
year = "2013",
abstract = "Several studies have linked mutations in the genes encoding cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1) to a reduced VKA dose requirement and an increased risk of bleeding. Nevertheless, implementation of genotyping as a routine practice is still controversial. Our study was conducted in order to investigate the impact of genetic factors, presence of VKORC1-c.1639A, CYP2C*2 and CYP2C*3 among outpatients referred to Anticoagulation Service due to extremely unstable anticoagulant therapy. From 2008 to 2011, 68 patients, mean age 65.9, were included in the study. They were referred from primary care physicians due to inability to sustain the therapeutic range in the period of initiation of anticoagulant therapy. Genotyping results showed that 17 (25 %) of them were carriers of both CYP2C9 and VKORC1 variant alleles, 38 (55.9 %) were carriers of VKORC1 c.1639AA, 6 (8.8 %) were carriers of CYP2C9 variant alleles, while 7 (10.3 %) of them were carriers of wild type alleles. INR control upon admission showed that 34 (50 %) of them were over-anticoagulated, while 12 (17.6 %) of them had subsequent bleeding complications. Among over-anticoagulated patients, 32 were carriers of mutated alleles in both CYP2C9 and VKORC1 gene or VKORC1 alone, while 2 of patients carried wild type alleles. In addition to presence of CYP2C9 or VKORC 1 alleles, older age was an important factor related to a lower dose and risk for over-anticoagulation. Genotype (CYP2C9/VKORC1) and age are the most important factors that could predispose an extreme response and subsequent bleeding complications during the initiation of VKA.",
publisher = "Springer, Dordrecht",
journal = "Journal of Thrombosis and Thrombolysis",
title = "Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation",
pages = "94-90",
number = "1",
volume = "35",
doi = "10.1007/s11239-012-0769-8"
}
Kovač, M., Rakićević, L., Kušić-Tišma, J.,& Radojković, D.. (2013). Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation. in Journal of Thrombosis and Thrombolysis
Springer, Dordrecht., 35(1), 90-94.
https://doi.org/10.1007/s11239-012-0769-8
Kovač M, Rakićević L, Kušić-Tišma J, Radojković D. Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation. in Journal of Thrombosis and Thrombolysis. 2013;35(1):90-94.
doi:10.1007/s11239-012-0769-8 .
Kovač, Mirjana, Rakićević, Ljiljana, Kušić-Tišma, Jelena, Radojković, Dragica, "Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation" in Journal of Thrombosis and Thrombolysis, 35, no. 1 (2013):90-94,
https://doi.org/10.1007/s11239-012-0769-8 . .
4
2
3

Rationalized DNA sequencing-based protocol for genotyping patients receiving coumarin therapy

Rakićević, Ljiljana; Kušić-Tišma, Jelena; Kovač, Mirjana; Backović, Dragana; Radojković, Dragica

(Taylor & Francis Ltd, Abingdon, 2013)

TY  - JOUR
AU  - Rakićević, Ljiljana
AU  - Kušić-Tišma, Jelena
AU  - Kovač, Mirjana
AU  - Backović, Dragana
AU  - Radojković, Dragica 
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/651
AB  - During the last decade genetic factors affecting coumarin therapy have been extensively investigated. The most important genes appear to be CYP2C9 and VKORC1, and different studies have shown that DNA testing can dramatically improve the safety and effectiveness of the therapy. However, the implementation of pharmacogenetic testing in everyday practice is still not a reality. Facilities and ability to get results before the start of therapy are very important. The implementation of specific methodology and equipment for particular type of diagnostics can represent a serious, even impossible, financial hurdle to overcome (especially in developing countries). For this reason, the use of every tool that contributes to rationalization of the existing methods can be a considerable asset. Therefore, we set the goal to rationalize our current DNA sequencing based protocol for analysis of the VKORC1 c.-1639G gt A, CYP2C9*2 and CYP2C9*3 variant alleles, in order to obtain shorter and easier procedure. Simplification of the protocol was achieved by setting up multiplex PCR and omitting DNA extraction. This rationalization of the existing DNA sequencing based procedure allows getting results in 12 hours. The new protocol was tested on 118 samples. Obtained results have shown full accordance to those obtained with previous, non-modified protocol. Therefore, given the circumstances, we consider that protocol for pharmocogenetic testing should be made more accessible - both to doctors and patients. It is one of the prerequisites in order to make genotyping prior to the therapy common practice.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Scandinavian Journal of Clinical & Laboratory Investigation
T1  - Rationalized DNA sequencing-based protocol for genotyping patients receiving coumarin therapy
EP  - 527
IS  - 6
SP  - 523
VL  - 73
DO  - 10.3109/00365513.2013.809142
ER  - 
@article{
author = "Rakićević, Ljiljana and Kušić-Tišma, Jelena and Kovač, Mirjana and Backović, Dragana and Radojković, Dragica ",
year = "2013",
abstract = "During the last decade genetic factors affecting coumarin therapy have been extensively investigated. The most important genes appear to be CYP2C9 and VKORC1, and different studies have shown that DNA testing can dramatically improve the safety and effectiveness of the therapy. However, the implementation of pharmacogenetic testing in everyday practice is still not a reality. Facilities and ability to get results before the start of therapy are very important. The implementation of specific methodology and equipment for particular type of diagnostics can represent a serious, even impossible, financial hurdle to overcome (especially in developing countries). For this reason, the use of every tool that contributes to rationalization of the existing methods can be a considerable asset. Therefore, we set the goal to rationalize our current DNA sequencing based protocol for analysis of the VKORC1 c.-1639G gt A, CYP2C9*2 and CYP2C9*3 variant alleles, in order to obtain shorter and easier procedure. Simplification of the protocol was achieved by setting up multiplex PCR and omitting DNA extraction. This rationalization of the existing DNA sequencing based procedure allows getting results in 12 hours. The new protocol was tested on 118 samples. Obtained results have shown full accordance to those obtained with previous, non-modified protocol. Therefore, given the circumstances, we consider that protocol for pharmocogenetic testing should be made more accessible - both to doctors and patients. It is one of the prerequisites in order to make genotyping prior to the therapy common practice.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Scandinavian Journal of Clinical & Laboratory Investigation",
title = "Rationalized DNA sequencing-based protocol for genotyping patients receiving coumarin therapy",
pages = "527-523",
number = "6",
volume = "73",
doi = "10.3109/00365513.2013.809142"
}
Rakićević, L., Kušić-Tišma, J., Kovač, M., Backović, D.,& Radojković, D.. (2013). Rationalized DNA sequencing-based protocol for genotyping patients receiving coumarin therapy. in Scandinavian Journal of Clinical & Laboratory Investigation
Taylor & Francis Ltd, Abingdon., 73(6), 523-527.
https://doi.org/10.3109/00365513.2013.809142
Rakićević L, Kušić-Tišma J, Kovač M, Backović D, Radojković D. Rationalized DNA sequencing-based protocol for genotyping patients receiving coumarin therapy. in Scandinavian Journal of Clinical & Laboratory Investigation. 2013;73(6):523-527.
doi:10.3109/00365513.2013.809142 .
Rakićević, Ljiljana, Kušić-Tišma, Jelena, Kovač, Mirjana, Backović, Dragana, Radojković, Dragica , "Rationalized DNA sequencing-based protocol for genotyping patients receiving coumarin therapy" in Scandinavian Journal of Clinical & Laboratory Investigation, 73, no. 6 (2013):523-527,
https://doi.org/10.3109/00365513.2013.809142 . .
1
1
1

Clinical characteristics of the first thrombosis process among young women and those over 45 years

Kovač, Mirjana; Mitić, G.; Miković, Z.; Mandić, V.; Rakićević, Ljiljana; Đorđević, Valentina; Radojković, Dragica

(Pergamon-Elsevier Science Ltd, Oxford, 2013)

TY  - CONF
AU  - Kovač, Mirjana
AU  - Mitić, G.
AU  - Miković, Z.
AU  - Mandić, V.
AU  - Rakićević, Ljiljana
AU  - Đorđević, Valentina
AU  - Radojković, Dragica
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/620
PB  - Pergamon-Elsevier Science Ltd, Oxford
C3  - Thrombosis Research
T1  - Clinical characteristics of the first thrombosis process among young women and those over 45 years
EP  - S86
SP  - S85
VL  - 131
DO  - 10.1016/S0049-3848(13)70080-X
ER  - 
@conference{
author = "Kovač, Mirjana and Mitić, G. and Miković, Z. and Mandić, V. and Rakićević, Ljiljana and Đorđević, Valentina and Radojković, Dragica",
year = "2013",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Thrombosis Research",
title = "Clinical characteristics of the first thrombosis process among young women and those over 45 years",
pages = "S86-S85",
volume = "131",
doi = "10.1016/S0049-3848(13)70080-X"
}
Kovač, M., Mitić, G., Miković, Z., Mandić, V., Rakićević, L., Đorđević, V.,& Radojković, D.. (2013). Clinical characteristics of the first thrombosis process among young women and those over 45 years. in Thrombosis Research
Pergamon-Elsevier Science Ltd, Oxford., 131, S85-S86.
https://doi.org/10.1016/S0049-3848(13)70080-X
Kovač M, Mitić G, Miković Z, Mandić V, Rakićević L, Đorđević V, Radojković D. Clinical characteristics of the first thrombosis process among young women and those over 45 years. in Thrombosis Research. 2013;131:S85-S86.
doi:10.1016/S0049-3848(13)70080-X .
Kovač, Mirjana, Mitić, G., Miković, Z., Mandić, V., Rakićević, Ljiljana, Đorđević, Valentina, Radojković, Dragica, "Clinical characteristics of the first thrombosis process among young women and those over 45 years" in Thrombosis Research, 131 (2013):S85-S86,
https://doi.org/10.1016/S0049-3848(13)70080-X . .

Prothrombotic Genetic Risk Factors in Stroke: A Possible Different Role in Pediatric and Adult Patients

Đorđević, Valentina; Stanković, Marija; Branković-Srecković, Vesna; Rakićević, Ljiljana; Damnjanović, Tatjana; Antonijević, Nebojša; Radojković, Dragica

(Sage Publications Inc, Thousand Oaks, 2012)

TY  - JOUR
AU  - Đorđević, Valentina
AU  - Stanković, Marija
AU  - Branković-Srecković, Vesna
AU  - Rakićević, Ljiljana
AU  - Damnjanović, Tatjana
AU  - Antonijević, Nebojša
AU  - Radojković, Dragica
PY  - 2012
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/596
AB  - The role of thrombophilia in the pathogenesis of stroke is still controversial, especially in the pediatric stroke. In order to examine the role of common thrombophilic mutations in children and adults with stroke, a case-control study was carried out in a group of 80 children and 73 younger adult patients. The control groups encompassed 100 healthy children and 120 healthy blood donors. Our results showed no significant differences in the frequency of factor V (FV) Leiden, FII G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T variants between patient groups and corresponding controls. According to our results, carriers of 677CT genotype have 3.62 higher risks to develop stroke in children than in adults (P  lt  .001). The obtained data indicate that heterozygosity for MTHFR C677T variant represents a possible important risk factor for pediatric stroke and suggest a different role of this gene variant in etiology of stroke in pediatric and adult patients.
PB  - Sage Publications Inc, Thousand Oaks
T2  - Clinical and Applied Thrombosis-Hemostasis
T1  - Prothrombotic Genetic Risk Factors in Stroke: A Possible Different Role in Pediatric and Adult Patients
EP  - 661
IS  - 6
SP  - 658
VL  - 18
DO  - 10.1177/1076029611432136
ER  - 
@article{
author = "Đorđević, Valentina and Stanković, Marija and Branković-Srecković, Vesna and Rakićević, Ljiljana and Damnjanović, Tatjana and Antonijević, Nebojša and Radojković, Dragica",
year = "2012",
abstract = "The role of thrombophilia in the pathogenesis of stroke is still controversial, especially in the pediatric stroke. In order to examine the role of common thrombophilic mutations in children and adults with stroke, a case-control study was carried out in a group of 80 children and 73 younger adult patients. The control groups encompassed 100 healthy children and 120 healthy blood donors. Our results showed no significant differences in the frequency of factor V (FV) Leiden, FII G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T variants between patient groups and corresponding controls. According to our results, carriers of 677CT genotype have 3.62 higher risks to develop stroke in children than in adults (P  lt  .001). The obtained data indicate that heterozygosity for MTHFR C677T variant represents a possible important risk factor for pediatric stroke and suggest a different role of this gene variant in etiology of stroke in pediatric and adult patients.",
publisher = "Sage Publications Inc, Thousand Oaks",
journal = "Clinical and Applied Thrombosis-Hemostasis",
title = "Prothrombotic Genetic Risk Factors in Stroke: A Possible Different Role in Pediatric and Adult Patients",
pages = "661-658",
number = "6",
volume = "18",
doi = "10.1177/1076029611432136"
}
Đorđević, V., Stanković, M., Branković-Srecković, V., Rakićević, L., Damnjanović, T., Antonijević, N.,& Radojković, D.. (2012). Prothrombotic Genetic Risk Factors in Stroke: A Possible Different Role in Pediatric and Adult Patients. in Clinical and Applied Thrombosis-Hemostasis
Sage Publications Inc, Thousand Oaks., 18(6), 658-661.
https://doi.org/10.1177/1076029611432136
Đorđević V, Stanković M, Branković-Srecković V, Rakićević L, Damnjanović T, Antonijević N, Radojković D. Prothrombotic Genetic Risk Factors in Stroke: A Possible Different Role in Pediatric and Adult Patients. in Clinical and Applied Thrombosis-Hemostasis. 2012;18(6):658-661.
doi:10.1177/1076029611432136 .
Đorđević, Valentina, Stanković, Marija, Branković-Srecković, Vesna, Rakićević, Ljiljana, Damnjanović, Tatjana, Antonijević, Nebojša, Radojković, Dragica, "Prothrombotic Genetic Risk Factors in Stroke: A Possible Different Role in Pediatric and Adult Patients" in Clinical and Applied Thrombosis-Hemostasis, 18, no. 6 (2012):658-661,
https://doi.org/10.1177/1076029611432136 . .
4
13
7
13

Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation

Kovač, Mirjana; Rakićević, Ljiljana; Kušić-Tišma, Jelena; Radojković, Dragica

(Pergamon-Elsevier Science Ltd, Oxford, 2012)

TY  - CONF
AU  - Kovač, Mirjana
AU  - Rakićević, Ljiljana
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica
PY  - 2012
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/591
PB  - Pergamon-Elsevier Science Ltd, Oxford
C3  - Thrombosis Research
T1  - Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation
EP  - S119
SP  - S119
VL  - 130
DO  - 10.1016/j.thromres.2012.08.051
ER  - 
@conference{
author = "Kovač, Mirjana and Rakićević, Ljiljana and Kušić-Tišma, Jelena and Radojković, Dragica",
year = "2012",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Thrombosis Research",
title = "Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation",
pages = "S119-S119",
volume = "130",
doi = "10.1016/j.thromres.2012.08.051"
}
Kovač, M., Rakićević, L., Kušić-Tišma, J.,& Radojković, D.. (2012). Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation. in Thrombosis Research
Pergamon-Elsevier Science Ltd, Oxford., 130, S119-S119.
https://doi.org/10.1016/j.thromres.2012.08.051
Kovač M, Rakićević L, Kušić-Tišma J, Radojković D. Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation. in Thrombosis Research. 2012;130:S119-S119.
doi:10.1016/j.thromres.2012.08.051 .
Kovač, Mirjana, Rakićević, Ljiljana, Kušić-Tišma, Jelena, Radojković, Dragica, "Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation" in Thrombosis Research, 130 (2012):S119-S119,
https://doi.org/10.1016/j.thromres.2012.08.051 . .

Prenatal diagnosis of hemophilia in Serbia: Evolution from phenotypic to molecular methods

Miković, D.; Janković, G.; Rakić, L.; Dolni-Car, M. Benedikt; Debeljak, M.; Rakićević, Ljiljana; Plecas, D.

(Wiley-Blackwell, Hoboken, 2012)

TY  - CONF
AU  - Miković, D.
AU  - Janković, G.
AU  - Rakić, L.
AU  - Dolni-Car, M. Benedikt
AU  - Debeljak, M.
AU  - Rakićević, Ljiljana
AU  - Plecas, D.
PY  - 2012
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/560
PB  - Wiley-Blackwell, Hoboken
C3  - Haemophilia
T1  - Prenatal diagnosis of hemophilia in Serbia: Evolution from phenotypic to molecular methods
EP  - 159
SP  - 159
VL  - 18
UR  - https://hdl.handle.net/21.15107/rcub_imagine_560
ER  - 
@conference{
author = "Miković, D. and Janković, G. and Rakić, L. and Dolni-Car, M. Benedikt and Debeljak, M. and Rakićević, Ljiljana and Plecas, D.",
year = "2012",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Haemophilia",
title = "Prenatal diagnosis of hemophilia in Serbia: Evolution from phenotypic to molecular methods",
pages = "159-159",
volume = "18",
url = "https://hdl.handle.net/21.15107/rcub_imagine_560"
}
Miković, D., Janković, G., Rakić, L., Dolni-Car, M. B., Debeljak, M., Rakićević, L.,& Plecas, D.. (2012). Prenatal diagnosis of hemophilia in Serbia: Evolution from phenotypic to molecular methods. in Haemophilia
Wiley-Blackwell, Hoboken., 18, 159-159.
https://hdl.handle.net/21.15107/rcub_imagine_560
Miković D, Janković G, Rakić L, Dolni-Car MB, Debeljak M, Rakićević L, Plecas D. Prenatal diagnosis of hemophilia in Serbia: Evolution from phenotypic to molecular methods. in Haemophilia. 2012;18:159-159.
https://hdl.handle.net/21.15107/rcub_imagine_560 .
Miković, D., Janković, G., Rakić, L., Dolni-Car, M. Benedikt, Debeljak, M., Rakićević, Ljiljana, Plecas, D., "Prenatal diagnosis of hemophilia in Serbia: Evolution from phenotypic to molecular methods" in Haemophilia, 18 (2012):159-159,
https://hdl.handle.net/21.15107/rcub_imagine_560 .

Mutacije FV Leiden, FII G20210A i MTHFR C677T kao faktori rizika za nastanak tromboze dubokih vena gornjih i donjih ekstremiteta

Đorđević, Valentina; Pruner, Iva; Rakićević, Ljiljana; Kovač, Mirjana; Miković, Danijela; Miljić, Predrag; Antonijević, Nebojša; Radojković, Dragica

(Društvo genetičara Srbije, Beograd, 2011)

TY  - JOUR
AU  - Đorđević, Valentina
AU  - Pruner, Iva
AU  - Rakićević, Ljiljana
AU  - Kovač, Mirjana
AU  - Miković, Danijela
AU  - Miljić, Predrag
AU  - Antonijević, Nebojša
AU  - Radojković, Dragica
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/505
AB  - Tromboze dubokih vena (TDV) su multifaktorijalno oboljenje koje se javlja sa učestalošću 1/1000 stanovnika godišnje. Mutacije FV Leiden, FII G20210A i MTHFR C677T predstavljaju genetske faktore za nastanak venskih tromboza. Cilj ove studije je da se utvrdi učestalost FV Leiden, FII G20210A i MTHFR C677T mutacija kod bolesnika sa TDV gornjih ili donjih ekstremiteta. Studija je obuhvatila 119 bolesnika podeljenih u dve grupe. Grupa bolesnika sa TDV donjih ekstremiteta brojila je 77, a grupa sa TDV gornjih ekstremiteta 42 bolesnika. Prisustvo FV Leiden, FII G20210A i MTHFR C677T mutacija dokazivano je umnožavanjem odgovarajućeg fragmenta gena pomoću lančane reakcije umnožavanja polimerazom i digestijom dobijenih fragmenata restrikcionim enzimima (PCR-RFLP).Učestalost FV Leiden mutacije, u grupi bolesnika sa TDV donjih ekstremiteta, iznosila je 26,0% u heterozigotnom obliku i 1,3% u homozigotnom obliku. U grupi bolesnika sa TDV gornjih ekstremiteta, učestalost heterozigotnih nosilaca iznosila je 7,2%. Mutacija FII G20210A bila je prisutna kod 15,6% ispitanika u grupi bolesnika sa TDV donjih ekstremiteta u heterozigotnom obliku, dok je u grupi sa TDV gornjih ekstremiteta ova mutacija bila zastupljena sa 7,2% u heterozigotnom i 2,3% u homozigotnom obliku. Učestalost MTHFR C677T mutacije kod bolesnika sa TDV donjih ekstremiteta iznosila je 42,8% u heterozigotnom obliku i 13% u homozigotnom obliku, a kod TDV gornjih ekstremiteta 52,4% u heterozigotnom obliku i 9,5% u homozigotnom obliku.Mutacije FV Leiden i FII G20210A predstavljaju značajne faktore rizika za nastanak TDV donjih ekstremiteta. Kod TDV gornjih ekstremiteta ove mutacije su manje zastupljene i potrebno je sprovesti dalja istraživanja koja obuhvataju veći broj bolesnika. MTHFR C677T mutacija je manje značajan faktor rizika i treba ga razmatrati samo u slučajevima kada se pojavljuje u kombinaciji sa drugim faktorima rizika.
AB  - Deep vein thrombosis (DVT) is a multifactorial disease that occurs with frequency of 1/1000 per year. The FV Leiden, FII G20210A and MTHFR C677T mutations represent genetic factors for the occurrence of vein thrombosis. The goal of this study was to determine the frequency of these mutations in patients with DVT of upper and lower limbs. The study encompassed 119 patients divided in two groups. The group of patients with the lower limbs thrombosis included 77 patients, while the upper limbs thrombosis group included 42 patients. The presence of FV Leiden, FII G20210A and MTHFR C677T mutations was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. In patients with DVT of lower limbs, the frequency of FV Leiden mutation was 26,0% in heterozygous form and 1,3% in homozygous form. In the group of patients with DVT of upper limbs, the frequency of heterozygous carriers was 7.2%. In patients with DVT of lower limbs, FII G20210A mutation occurred in heterozygous form in 15.6% subjects, and in the group with DVT of upper limbs the frequency was 7.2% in heterozygous and 2.3% in homozygous form. The frequency of MTHFR C677T mutation in patients with lower limbs DVT was 42.8% in heterozygous form and 13% in homozygous form, while in the group of patients with upper limbs DVT, the frequency was 52.4% in heterozygous form and 9.5% in homozygous form. The FV Leiden and FII G20210A mutations represent significant risk factors for the occurrence of DVT of lower limbs. These mutations are less frequent in DVT of upper limbs and more extensive further studies are needed to determine their potential role. The MTHFR C677T mutation represents less significant risk factor for lower limb DVT and should be taken into account only in cases when it occurs in combination with other risk factors.
PB  - Društvo genetičara Srbije, Beograd
T2  - Genetika-Belgrade
T1  - Mutacije FV Leiden, FII G20210A i MTHFR C677T kao faktori rizika za nastanak tromboze dubokih vena gornjih i donjih ekstremiteta
T1  - FV Leiden, FII G20210A and MTHFR C677T mutations in patients with lower or upper limb deep vein thrombosis
EP  - 380
IS  - 2
SP  - 371
VL  - 43
DO  - 10.2298/GENSR1102371D
ER  - 
@article{
author = "Đorđević, Valentina and Pruner, Iva and Rakićević, Ljiljana and Kovač, Mirjana and Miković, Danijela and Miljić, Predrag and Antonijević, Nebojša and Radojković, Dragica",
year = "2011",
abstract = "Tromboze dubokih vena (TDV) su multifaktorijalno oboljenje koje se javlja sa učestalošću 1/1000 stanovnika godišnje. Mutacije FV Leiden, FII G20210A i MTHFR C677T predstavljaju genetske faktore za nastanak venskih tromboza. Cilj ove studije je da se utvrdi učestalost FV Leiden, FII G20210A i MTHFR C677T mutacija kod bolesnika sa TDV gornjih ili donjih ekstremiteta. Studija je obuhvatila 119 bolesnika podeljenih u dve grupe. Grupa bolesnika sa TDV donjih ekstremiteta brojila je 77, a grupa sa TDV gornjih ekstremiteta 42 bolesnika. Prisustvo FV Leiden, FII G20210A i MTHFR C677T mutacija dokazivano je umnožavanjem odgovarajućeg fragmenta gena pomoću lančane reakcije umnožavanja polimerazom i digestijom dobijenih fragmenata restrikcionim enzimima (PCR-RFLP).Učestalost FV Leiden mutacije, u grupi bolesnika sa TDV donjih ekstremiteta, iznosila je 26,0% u heterozigotnom obliku i 1,3% u homozigotnom obliku. U grupi bolesnika sa TDV gornjih ekstremiteta, učestalost heterozigotnih nosilaca iznosila je 7,2%. Mutacija FII G20210A bila je prisutna kod 15,6% ispitanika u grupi bolesnika sa TDV donjih ekstremiteta u heterozigotnom obliku, dok je u grupi sa TDV gornjih ekstremiteta ova mutacija bila zastupljena sa 7,2% u heterozigotnom i 2,3% u homozigotnom obliku. Učestalost MTHFR C677T mutacije kod bolesnika sa TDV donjih ekstremiteta iznosila je 42,8% u heterozigotnom obliku i 13% u homozigotnom obliku, a kod TDV gornjih ekstremiteta 52,4% u heterozigotnom obliku i 9,5% u homozigotnom obliku.Mutacije FV Leiden i FII G20210A predstavljaju značajne faktore rizika za nastanak TDV donjih ekstremiteta. Kod TDV gornjih ekstremiteta ove mutacije su manje zastupljene i potrebno je sprovesti dalja istraživanja koja obuhvataju veći broj bolesnika. MTHFR C677T mutacija je manje značajan faktor rizika i treba ga razmatrati samo u slučajevima kada se pojavljuje u kombinaciji sa drugim faktorima rizika., Deep vein thrombosis (DVT) is a multifactorial disease that occurs with frequency of 1/1000 per year. The FV Leiden, FII G20210A and MTHFR C677T mutations represent genetic factors for the occurrence of vein thrombosis. The goal of this study was to determine the frequency of these mutations in patients with DVT of upper and lower limbs. The study encompassed 119 patients divided in two groups. The group of patients with the lower limbs thrombosis included 77 patients, while the upper limbs thrombosis group included 42 patients. The presence of FV Leiden, FII G20210A and MTHFR C677T mutations was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. In patients with DVT of lower limbs, the frequency of FV Leiden mutation was 26,0% in heterozygous form and 1,3% in homozygous form. In the group of patients with DVT of upper limbs, the frequency of heterozygous carriers was 7.2%. In patients with DVT of lower limbs, FII G20210A mutation occurred in heterozygous form in 15.6% subjects, and in the group with DVT of upper limbs the frequency was 7.2% in heterozygous and 2.3% in homozygous form. The frequency of MTHFR C677T mutation in patients with lower limbs DVT was 42.8% in heterozygous form and 13% in homozygous form, while in the group of patients with upper limbs DVT, the frequency was 52.4% in heterozygous form and 9.5% in homozygous form. The FV Leiden and FII G20210A mutations represent significant risk factors for the occurrence of DVT of lower limbs. These mutations are less frequent in DVT of upper limbs and more extensive further studies are needed to determine their potential role. The MTHFR C677T mutation represents less significant risk factor for lower limb DVT and should be taken into account only in cases when it occurs in combination with other risk factors.",
publisher = "Društvo genetičara Srbije, Beograd",
journal = "Genetika-Belgrade",
title = "Mutacije FV Leiden, FII G20210A i MTHFR C677T kao faktori rizika za nastanak tromboze dubokih vena gornjih i donjih ekstremiteta, FV Leiden, FII G20210A and MTHFR C677T mutations in patients with lower or upper limb deep vein thrombosis",
pages = "380-371",
number = "2",
volume = "43",
doi = "10.2298/GENSR1102371D"
}
Đorđević, V., Pruner, I., Rakićević, L., Kovač, M., Miković, D., Miljić, P., Antonijević, N.,& Radojković, D.. (2011). Mutacije FV Leiden, FII G20210A i MTHFR C677T kao faktori rizika za nastanak tromboze dubokih vena gornjih i donjih ekstremiteta. in Genetika-Belgrade
Društvo genetičara Srbije, Beograd., 43(2), 371-380.
https://doi.org/10.2298/GENSR1102371D
Đorđević V, Pruner I, Rakićević L, Kovač M, Miković D, Miljić P, Antonijević N, Radojković D. Mutacije FV Leiden, FII G20210A i MTHFR C677T kao faktori rizika za nastanak tromboze dubokih vena gornjih i donjih ekstremiteta. in Genetika-Belgrade. 2011;43(2):371-380.
doi:10.2298/GENSR1102371D .
Đorđević, Valentina, Pruner, Iva, Rakićević, Ljiljana, Kovač, Mirjana, Miković, Danijela, Miljić, Predrag, Antonijević, Nebojša, Radojković, Dragica, "Mutacije FV Leiden, FII G20210A i MTHFR C677T kao faktori rizika za nastanak tromboze dubokih vena gornjih i donjih ekstremiteta" in Genetika-Belgrade, 43, no. 2 (2011):371-380,
https://doi.org/10.2298/GENSR1102371D . .
5
2
6

Extreme sensitivity to acenocoumarol therapy in patient with both VKORC.-1639 A/A and CYP2C9*1/*3 genotypes

Kovač, Mirjana; Rakićević, Ljiljana; Radojković, Dragica

(Springer, Dordrecht, 2011)

TY  - JOUR
AU  - Kovač, Mirjana
AU  - Rakićević, Ljiljana
AU  - Radojković, Dragica 
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/498
AB  - The initiation phase of vitamin K antagonist (VKA) is a challenging and demanding process that can result in adverse event such as bleeding. Dosing is influenced by a variety of acquired factors, while another factor that is associated with the optimal dose is the presence of certain genetic variants. We describe a 73 years old male who required extremely low dose of acenocoumarol (0.33 mg/day) to reach the target INR of 2-2.5. During initiation of VKA he started with usually recommended doses of acenocoumarol: 4 mg/day for the first 2 days and 3 mg/day during next 2 days. On fifth day of initiation, massive haematuria occurred and INR level of 10.5 was recorded. Patient was transfused with three doses of fresh frozen plasma in order to stop the bleeding. Acenocoumarol dose was gradually reduced after every INR laboratory monitoring and finally a dose of 0.33 mg/day was required for maintain stable anticoagulation. The genotyping results performed after introducing of VKA showed the patient was homozygous for vitamin K epoxide reductase (VKORC1) c.-1639 G  gt  A, and heterozygous for cytochrome P450 2C9 (CYP2C9)*3 which pointed to extreme sensitivity to acenocoumarol. Our case supports the need for prospective genotyping of CYP2C9 and VKORC1 prior to initiation of VKA where pharmacogenetics, as a good predictor of extreme sensitivity to VKA, could help to tailor optimal VKA dose.
PB  - Springer, Dordrecht
T2  - Journal of Thrombosis and Thrombolysis
T1  - Extreme sensitivity to acenocoumarol therapy in patient with both VKORC.-1639 A/A and CYP2C9*1/*3 genotypes
EP  - 371
IS  - 3
SP  - 368
VL  - 32
DO  - 10.1007/s11239-011-0601-x
ER  - 
@article{
author = "Kovač, Mirjana and Rakićević, Ljiljana and Radojković, Dragica ",
year = "2011",
abstract = "The initiation phase of vitamin K antagonist (VKA) is a challenging and demanding process that can result in adverse event such as bleeding. Dosing is influenced by a variety of acquired factors, while another factor that is associated with the optimal dose is the presence of certain genetic variants. We describe a 73 years old male who required extremely low dose of acenocoumarol (0.33 mg/day) to reach the target INR of 2-2.5. During initiation of VKA he started with usually recommended doses of acenocoumarol: 4 mg/day for the first 2 days and 3 mg/day during next 2 days. On fifth day of initiation, massive haematuria occurred and INR level of 10.5 was recorded. Patient was transfused with three doses of fresh frozen plasma in order to stop the bleeding. Acenocoumarol dose was gradually reduced after every INR laboratory monitoring and finally a dose of 0.33 mg/day was required for maintain stable anticoagulation. The genotyping results performed after introducing of VKA showed the patient was homozygous for vitamin K epoxide reductase (VKORC1) c.-1639 G  gt  A, and heterozygous for cytochrome P450 2C9 (CYP2C9)*3 which pointed to extreme sensitivity to acenocoumarol. Our case supports the need for prospective genotyping of CYP2C9 and VKORC1 prior to initiation of VKA where pharmacogenetics, as a good predictor of extreme sensitivity to VKA, could help to tailor optimal VKA dose.",
publisher = "Springer, Dordrecht",
journal = "Journal of Thrombosis and Thrombolysis",
title = "Extreme sensitivity to acenocoumarol therapy in patient with both VKORC.-1639 A/A and CYP2C9*1/*3 genotypes",
pages = "371-368",
number = "3",
volume = "32",
doi = "10.1007/s11239-011-0601-x"
}
Kovač, M., Rakićević, L.,& Radojković, D.. (2011). Extreme sensitivity to acenocoumarol therapy in patient with both VKORC.-1639 A/A and CYP2C9*1/*3 genotypes. in Journal of Thrombosis and Thrombolysis
Springer, Dordrecht., 32(3), 368-371.
https://doi.org/10.1007/s11239-011-0601-x
Kovač M, Rakićević L, Radojković D. Extreme sensitivity to acenocoumarol therapy in patient with both VKORC.-1639 A/A and CYP2C9*1/*3 genotypes. in Journal of Thrombosis and Thrombolysis. 2011;32(3):368-371.
doi:10.1007/s11239-011-0601-x .
Kovač, Mirjana, Rakićević, Ljiljana, Radojković, Dragica , "Extreme sensitivity to acenocoumarol therapy in patient with both VKORC.-1639 A/A and CYP2C9*1/*3 genotypes" in Journal of Thrombosis and Thrombolysis, 32, no. 3 (2011):368-371,
https://doi.org/10.1007/s11239-011-0601-x . .
8
6
7

The expression of Muscle ankyrin repeat proteins in brown adipose tissue

Rakićević, Ljiljana; Petrović, Nataša; Radojković, Dragica; Kojić, Snežana

(Srpsko biološko društvo, Beograd, i dr., 2011)

TY  - JOUR
AU  - Rakićević, Ljiljana
AU  - Petrović, Nataša
AU  - Radojković, Dragica
AU  - Kojić, Snežana
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/497
AB  - MARP family members CARP, Ankrd2 and DARP are expressed in the striated muscle, while DARP protein is also detected in brown adipose tissue (BAT). Taking into account recent findings concerning the common origin of muscle and brown fat, expression of CARP and Ankrd2 in mouse BAT was investigated. We demonstrated Ankrd2 expression in both inactive and thermogenically active BAT, while CARP expression was not detected. Our findings suggest that the expression of Ankrd2 in BAT could be a part of the 'myogenic transcriptional signature', further supporting the evidence that muscle and brown adipose cells arise from the same myoblastic precursor.
PB  - Srpsko biološko društvo, Beograd, i dr.
T2  - Archives of Biological Sciences
T1  - The expression of Muscle ankyrin repeat proteins in brown adipose tissue
EP  - 920
IS  - 4
SP  - 915
VL  - 63
DO  - 10.2298/ABS1104915R
ER  - 
@article{
author = "Rakićević, Ljiljana and Petrović, Nataša and Radojković, Dragica and Kojić, Snežana",
year = "2011",
abstract = "MARP family members CARP, Ankrd2 and DARP are expressed in the striated muscle, while DARP protein is also detected in brown adipose tissue (BAT). Taking into account recent findings concerning the common origin of muscle and brown fat, expression of CARP and Ankrd2 in mouse BAT was investigated. We demonstrated Ankrd2 expression in both inactive and thermogenically active BAT, while CARP expression was not detected. Our findings suggest that the expression of Ankrd2 in BAT could be a part of the 'myogenic transcriptional signature', further supporting the evidence that muscle and brown adipose cells arise from the same myoblastic precursor.",
publisher = "Srpsko biološko društvo, Beograd, i dr.",
journal = "Archives of Biological Sciences",
title = "The expression of Muscle ankyrin repeat proteins in brown adipose tissue",
pages = "920-915",
number = "4",
volume = "63",
doi = "10.2298/ABS1104915R"
}
Rakićević, L., Petrović, N., Radojković, D.,& Kojić, S.. (2011). The expression of Muscle ankyrin repeat proteins in brown adipose tissue. in Archives of Biological Sciences
Srpsko biološko društvo, Beograd, i dr.., 63(4), 915-920.
https://doi.org/10.2298/ABS1104915R
Rakićević L, Petrović N, Radojković D, Kojić S. The expression of Muscle ankyrin repeat proteins in brown adipose tissue. in Archives of Biological Sciences. 2011;63(4):915-920.
doi:10.2298/ABS1104915R .
Rakićević, Ljiljana, Petrović, Nataša, Radojković, Dragica, Kojić, Snežana, "The expression of Muscle ankyrin repeat proteins in brown adipose tissue" in Archives of Biological Sciences, 63, no. 4 (2011):915-920,
https://doi.org/10.2298/ABS1104915R . .

Multi-Tasking Role of the Mechanosensing Protein Ankrd2 in the Signaling Network of Striated Muscle

Belgrano, Anna; Rakićević, Ljiljana; Mittempergher, Lorenza; Campanaro, Stefano; Martinelli, Valentina C.; Mouly, Vincent; Valle, Giorgio; Kojić, Snežana; Faulkner, Georgine

(Public Library Science, San Francisco, 2011)

TY  - JOUR
AU  - Belgrano, Anna
AU  - Rakićević, Ljiljana
AU  - Mittempergher, Lorenza
AU  - Campanaro, Stefano
AU  - Martinelli, Valentina C.
AU  - Mouly, Vincent
AU  - Valle, Giorgio
AU  - Kojić, Snežana
AU  - Faulkner, Georgine
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/502
AB  - Background: Ankrd2 (also known as Arpp) together with Ankrd1/CARP and DARP are members of the MARP mechanosensing proteins that form a complex with titin (N2A)/calpain 3 protease/myopalladin. In muscle, Ankrd2 is located in the I-band of the sarcomere and moves to the nucleus of adjacent myofibers on muscle injury. In myoblasts it is predominantly in the nucleus and on differentiation shifts from the nucleus to the cytoplasm. In agreement with its role as a sensor it interacts both with sarcomeric proteins and transcription factors. Methodology/Principal Findings: Expression profiling of endogenous Ankrd2 silenced in human myotubes was undertaken to elucidate its role as an intermediary in cell signaling pathways. Silencing Ankrd2 expression altered the expression of genes involved in both intercellular communication (cytokine-cytokine receptor interaction, endocytosis, focal adhesion, tight junction, gap junction and regulation of the actin cytoskeleton) and intracellular communication (calcium, insulin, MAPK, p53, TGF-beta and Wnt signaling). The significance of Ankrd2 in cell signaling was strengthened by the fact that we were able to show for the first time that Nkx2.5 and p53 are upstream effectors of the Ankrd2 gene and that Ankrd1/CARP, another MARP member, can modulate the transcriptional ability of MyoD on the Ankrd2 promoter. Another novel finding was the interaction between Ankrd2 and proteins with PDZ and SH3 domains, further supporting its role in signaling. It is noteworthy that we demonstrated that transcription factors PAX6, LHX2, NFIL3 and MECP2, were able to bind both the Ankrd2 protein and its promoter indicating the presence of a regulatory feedback loop mechanism. Conclusions/Significance: In conclusion we demonstrate that Ankrd2 is a potent regulator in muscle cells affecting a multitude of pathways and processes.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - Multi-Tasking Role of the Mechanosensing Protein Ankrd2 in the Signaling Network of Striated Muscle
IS  - 10
VL  - 6
DO  - 10.1371/journal.pone.0025519
ER  - 
@article{
author = "Belgrano, Anna and Rakićević, Ljiljana and Mittempergher, Lorenza and Campanaro, Stefano and Martinelli, Valentina C. and Mouly, Vincent and Valle, Giorgio and Kojić, Snežana and Faulkner, Georgine",
year = "2011",
abstract = "Background: Ankrd2 (also known as Arpp) together with Ankrd1/CARP and DARP are members of the MARP mechanosensing proteins that form a complex with titin (N2A)/calpain 3 protease/myopalladin. In muscle, Ankrd2 is located in the I-band of the sarcomere and moves to the nucleus of adjacent myofibers on muscle injury. In myoblasts it is predominantly in the nucleus and on differentiation shifts from the nucleus to the cytoplasm. In agreement with its role as a sensor it interacts both with sarcomeric proteins and transcription factors. Methodology/Principal Findings: Expression profiling of endogenous Ankrd2 silenced in human myotubes was undertaken to elucidate its role as an intermediary in cell signaling pathways. Silencing Ankrd2 expression altered the expression of genes involved in both intercellular communication (cytokine-cytokine receptor interaction, endocytosis, focal adhesion, tight junction, gap junction and regulation of the actin cytoskeleton) and intracellular communication (calcium, insulin, MAPK, p53, TGF-beta and Wnt signaling). The significance of Ankrd2 in cell signaling was strengthened by the fact that we were able to show for the first time that Nkx2.5 and p53 are upstream effectors of the Ankrd2 gene and that Ankrd1/CARP, another MARP member, can modulate the transcriptional ability of MyoD on the Ankrd2 promoter. Another novel finding was the interaction between Ankrd2 and proteins with PDZ and SH3 domains, further supporting its role in signaling. It is noteworthy that we demonstrated that transcription factors PAX6, LHX2, NFIL3 and MECP2, were able to bind both the Ankrd2 protein and its promoter indicating the presence of a regulatory feedback loop mechanism. Conclusions/Significance: In conclusion we demonstrate that Ankrd2 is a potent regulator in muscle cells affecting a multitude of pathways and processes.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "Multi-Tasking Role of the Mechanosensing Protein Ankrd2 in the Signaling Network of Striated Muscle",
number = "10",
volume = "6",
doi = "10.1371/journal.pone.0025519"
}
Belgrano, A., Rakićević, L., Mittempergher, L., Campanaro, S., Martinelli, V. C., Mouly, V., Valle, G., Kojić, S.,& Faulkner, G.. (2011). Multi-Tasking Role of the Mechanosensing Protein Ankrd2 in the Signaling Network of Striated Muscle. in PLoS One
Public Library Science, San Francisco., 6(10).
https://doi.org/10.1371/journal.pone.0025519
Belgrano A, Rakićević L, Mittempergher L, Campanaro S, Martinelli VC, Mouly V, Valle G, Kojić S, Faulkner G. Multi-Tasking Role of the Mechanosensing Protein Ankrd2 in the Signaling Network of Striated Muscle. in PLoS One. 2011;6(10).
doi:10.1371/journal.pone.0025519 .
Belgrano, Anna, Rakićević, Ljiljana, Mittempergher, Lorenza, Campanaro, Stefano, Martinelli, Valentina C., Mouly, Vincent, Valle, Giorgio, Kojić, Snežana, Faulkner, Georgine, "Multi-Tasking Role of the Mechanosensing Protein Ankrd2 in the Signaling Network of Striated Muscle" in PLoS One, 6, no. 10 (2011),
https://doi.org/10.1371/journal.pone.0025519 . .
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