TY  - JOUR
AU  - Stanković, Marija
AU  - Kojić, Snežana
AU  - Đorđević, Valentina
AU  - Tomović, Andrija
AU  - Nagorni-Obradović, Ljudmila
AU  - Petrović-Stanojević, Nataša
AU  - Mitić-Milikić, Marija
AU  - Radojković, Dragica
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/901
AB  - The aetiology of chronic obstructive pulmonary disease (COPD) is complex. While cigarette smoking is a well-established cause of COPD, a myriad of assessed genetic factors has given conflicting data. Since gene-environment interactions are thought to be implicated in aetiopathogenesis of COPD, we aimed to examine the matrix metalloproteinase (MMP) 9 C-1562T (rs3918242) functional variant and cigarette smoke in the pathogenesis of this disease. The distribution of the MMP9 C-1562T variant was analyzed in COPD patients and controls with normal pulmonary function from Serbia. Interaction between the C-1562T genetic variant and cigarette smoking was assessed using a case-control model. The response of the C-1562T promoter variant to cigarette smoke condensate (CSC) exposure was examined using a dual luciferase reporter assay. The frequency of T allele carriers was higher in the COPD group than in smoker controls (38.4% vs. 20%; OR=2.7, P=0.027). Interaction between the T allele and cigarette smoking was identified in COPD occurrence (OR=4.38, P=0.005) and severity (P=0.001). A functional analysis of the C-1562T variant demonstrated a dose-dependent and allele-specific response (P lt 0.01) to CSC. Significantly higher MMP9 promoter activity following CSC exposure was found for the promoter harboring the T allele compared to the promoter harboring the C allele (P lt 0.05). Our study is the first to reveal an interaction between the MMP9-1562T allele and cigarette smoke in COPD, emphasising gene-environment interactions as a possible cause of lung damage in the pathogenesis of COPD. Environ. Mol. Mutagen. 57:447-454, 2016.
PB  - Wiley, Hoboken
T2  - Environmental and Molecular Mutagenesis
T1  - Gene-environment interaction between the MMP9 C-1562T promoter variant and cigarette smoke in the pathogenesis of chronic obstructive pulmonary disease
EP  - 454
IS  - 6
SP  - 447
VL  - 57
DO  - 10.1002/em.22025
ER  - 

@article{
author = "Stanković, Marija and Kojić, Snežana and Đorđević, Valentina and Tomović, Andrija and Nagorni-Obradović, Ljudmila and Petrović-Stanojević, Nataša and Mitić-Milikić, Marija and Radojković, Dragica",
year = "2016",
abstract = "The aetiology of chronic obstructive pulmonary disease (COPD) is complex. While cigarette smoking is a well-established cause of COPD, a myriad of assessed genetic factors has given conflicting data. Since gene-environment interactions are thought to be implicated in aetiopathogenesis of COPD, we aimed to examine the matrix metalloproteinase (MMP) 9 C-1562T (rs3918242) functional variant and cigarette smoke in the pathogenesis of this disease. The distribution of the MMP9 C-1562T variant was analyzed in COPD patients and controls with normal pulmonary function from Serbia. Interaction between the C-1562T genetic variant and cigarette smoking was assessed using a case-control model. The response of the C-1562T promoter variant to cigarette smoke condensate (CSC) exposure was examined using a dual luciferase reporter assay. The frequency of T allele carriers was higher in the COPD group than in smoker controls (38.4% vs. 20%; OR=2.7, P=0.027). Interaction between the T allele and cigarette smoking was identified in COPD occurrence (OR=4.38, P=0.005) and severity (P=0.001). A functional analysis of the C-1562T variant demonstrated a dose-dependent and allele-specific response (P lt 0.01) to CSC. Significantly higher MMP9 promoter activity following CSC exposure was found for the promoter harboring the T allele compared to the promoter harboring the C allele (P lt 0.05). Our study is the first to reveal an interaction between the MMP9-1562T allele and cigarette smoke in COPD, emphasising gene-environment interactions as a possible cause of lung damage in the pathogenesis of COPD. Environ. Mol. Mutagen. 57:447-454, 2016.",
publisher = "Wiley, Hoboken",
journal = "Environmental and Molecular Mutagenesis",
title = "Gene-environment interaction between the MMP9 C-1562T promoter variant and cigarette smoke in the pathogenesis of chronic obstructive pulmonary disease",
pages = "454-447",
number = "6",
volume = "57",
doi = "10.1002/em.22025"
}

Stanković, M., Kojić, S., Đorđević, V., Tomović, A., Nagorni-Obradović, L., Petrović-Stanojević, N., Mitić-Milikić, M.,& Radojković, D.. (2016). Gene-environment interaction between the MMP9 C-1562T promoter variant and cigarette smoke in the pathogenesis of chronic obstructive pulmonary disease. in Environmental and Molecular Mutagenesis
Wiley, Hoboken., 57(6), 447-454.
https://doi.org/10.1002/em.22025

Stanković M, Kojić S, Đorđević V, Tomović A, Nagorni-Obradović L, Petrović-Stanojević N, Mitić-Milikić M, Radojković D. Gene-environment interaction between the MMP9 C-1562T promoter variant and cigarette smoke in the pathogenesis of chronic obstructive pulmonary disease. in Environmental and Molecular Mutagenesis. 2016;57(6):447-454.
doi:10.1002/em.22025 .

Stanković, Marija, Kojić, Snežana, Đorđević, Valentina, Tomović, Andrija, Nagorni-Obradović, Ljudmila, Petrović-Stanojević, Nataša, Mitić-Milikić, Marija, Radojković, Dragica, "Gene-environment interaction between the MMP9 C-1562T promoter variant and cigarette smoke in the pathogenesis of chronic obstructive pulmonary disease" in Environmental and Molecular Mutagenesis, 57, no. 6 (2016):447-454,
https://doi.org/10.1002/em.22025 . .

TY  - JOUR
AU  - Stanković, Marija
AU  - Nikolić, Aleksandra
AU  - Tomović, Andrija
AU  - Mitić-Milikić, Marija
AU  - Nagorni-Obradović, Ljudmila
AU  - Petrović-Stanojević, Nataša
AU  - Radojković, Dragica
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/849
AB  - Uvod: Hronična opstruktivna bolest pluća (HOBP) jeste složeno oboljenje koje karakteriše povišen oksidativni stres. Funkcionalne varijante gena faze I i II ksenobiotičkog metabolizma mogu uticati na ravnotežu oksidanti-antioksidanti i mogu dovesti do razvoja HOBP. Cilj ove studije je bio ispitivanje uloge funkcionalnih genskih varijanti u genima za citohrom P450 (CYP), glutation S-transferazu (GST) i mikrozomalnu epoksidnu hidrolazu (mEH) u patogenezi HOBP u srpskoj populaciji. Metode: U ovoj studiji analizirane su genske varijante CYP1A1 *1A/*2A, CYP2E1 *1A/*5B, GSTM1 null, GSTT1 null, GSTP1 Ile105Val, mEH Tyr113His i mEH His139Arg u grupi obolelih od HOBP koja je obuhvatala 122 ispitanika i kontrolnoj grupi koja je obuhvatala 100 ispitanika sa normalnom funkcijom pluća. Rezultati: Dobijeni rezultati su pokazali da je GSTM1 null varijanta statistički značajno povišena u grupi obolelih od HOBP u poređenju sa kontrolnom grupom (61,5% i 47,0%; or = 1,80; p = 0,042). Takođe, uočena je značajna razlika u zastupljenosti kombinacije genotipova GSTM1 null i GSTP1 105Val/(Val) (38,5% i 24,0%; or = 1,98; p = 0,029), kao i kombinacije CYP1A1 *1A/*2A, GSTM1 null i mEH 113H is/(H is) (7,4% i 1,0% ; or = 7 ,88; p = 0,025). Zaključak: Ovo su prvi podaci o ulozi genskih varijanti gena faze I i II u patogenezi HOBP u srpskoj populaciji. Rezultati dobijeni u ovoj studiji otvaraju mogućnost za detaljniju analizu uloge genetičkih faktora u HOBP na većim grupama ispitanika. Pored toga, podaci dobijeni u našoj studiji potvrđuju važnost genetičkih determinanti povezanih sa HOBP u prethodnim studijama, ali takođe otkrivaju nove genetičke faktore, koji nisu objavljeni do sada.
AB  - Background: Chronic obstructive pulmonary disease (COPD) is a complex disorder characterized by increased oxidative stress. Functional genetic variants of phase I and II genes are implicated in oxidants-antioxidants imbalance and may be involved in COPD development. In this study, we aimed to investigate the role of cytochrome P450 (CYP), glutathione S-transferase (GST) and microsomal epoxide hydrolase (mEH) functional variants in the pathogenesis of COPD in a Serbian population. Methods: The genotypes of l2 2 COPD patients and 100 controls with normal lung function were determined for CYP1A1 *1A /*2A , CYP2E1 *1 A /*5B , GSTM1 null, GSTT1 null GSTP1 Ile105Val, mEH Tyr113His and mEH His139Arg gene variants. Results: Results obtained showed that GSTM1 null variant was significantly more represented in COPD patients than in controls (61.5% vs. 47.0%; or = 1.80; p = 0.042). Also, a significant difference was observed for combinations of GSTM1 null and GSTP1 105Val/(Val) (38.5% vs. 24.0%; or = 1.98; p = 0.029), as well as for CYP1A1 *1A/*2A, GSTM1 null and mEH 113His/(His) genotypes (7.4% vs. 1.0%; or = 7.88; p = 0.025). Conclusions: These are the first data concerning the analysis of the variants of phase I and II genes in the pathogenesis of COPD in a Serbian population. Results obtained in this study open up the possibility for thorough analyses of the role of genetic factors in COPD on larger cohorts. Also, they implicate the importance of previously described genetic associations with COPD in our population, as well as reveal a new one, not reported so far.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Udruženost funkcionalnih varijanti gena faze I I II sa hroničnom opstruktivnom bolešću pluća u srpskoj populaciji
T1  - Association of functional variants of phase I and II genes with chronic obstructive pulmonary disease in a Serbian population
EP  - 214
IS  - 2
SP  - 207
VL  - 34
DO  - 10.2478/jomb-2014-0024
ER  - 

@article{
author = "Stanković, Marija and Nikolić, Aleksandra and Tomović, Andrija and Mitić-Milikić, Marija and Nagorni-Obradović, Ljudmila and Petrović-Stanojević, Nataša and Radojković, Dragica",
year = "2015",
abstract = "Uvod: Hronična opstruktivna bolest pluća (HOBP) jeste složeno oboljenje koje karakteriše povišen oksidativni stres. Funkcionalne varijante gena faze I i II ksenobiotičkog metabolizma mogu uticati na ravnotežu oksidanti-antioksidanti i mogu dovesti do razvoja HOBP. Cilj ove studije je bio ispitivanje uloge funkcionalnih genskih varijanti u genima za citohrom P450 (CYP), glutation S-transferazu (GST) i mikrozomalnu epoksidnu hidrolazu (mEH) u patogenezi HOBP u srpskoj populaciji. Metode: U ovoj studiji analizirane su genske varijante CYP1A1 *1A/*2A, CYP2E1 *1A/*5B, GSTM1 null, GSTT1 null, GSTP1 Ile105Val, mEH Tyr113His i mEH His139Arg u grupi obolelih od HOBP koja je obuhvatala 122 ispitanika i kontrolnoj grupi koja je obuhvatala 100 ispitanika sa normalnom funkcijom pluća. Rezultati: Dobijeni rezultati su pokazali da je GSTM1 null varijanta statistički značajno povišena u grupi obolelih od HOBP u poređenju sa kontrolnom grupom (61,5% i 47,0%; or = 1,80; p = 0,042). Takođe, uočena je značajna razlika u zastupljenosti kombinacije genotipova GSTM1 null i GSTP1 105Val/(Val) (38,5% i 24,0%; or = 1,98; p = 0,029), kao i kombinacije CYP1A1 *1A/*2A, GSTM1 null i mEH 113H is/(H is) (7,4% i 1,0% ; or = 7 ,88; p = 0,025). Zaključak: Ovo su prvi podaci o ulozi genskih varijanti gena faze I i II u patogenezi HOBP u srpskoj populaciji. Rezultati dobijeni u ovoj studiji otvaraju mogućnost za detaljniju analizu uloge genetičkih faktora u HOBP na većim grupama ispitanika. Pored toga, podaci dobijeni u našoj studiji potvrđuju važnost genetičkih determinanti povezanih sa HOBP u prethodnim studijama, ali takođe otkrivaju nove genetičke faktore, koji nisu objavljeni do sada., Background: Chronic obstructive pulmonary disease (COPD) is a complex disorder characterized by increased oxidative stress. Functional genetic variants of phase I and II genes are implicated in oxidants-antioxidants imbalance and may be involved in COPD development. In this study, we aimed to investigate the role of cytochrome P450 (CYP), glutathione S-transferase (GST) and microsomal epoxide hydrolase (mEH) functional variants in the pathogenesis of COPD in a Serbian population. Methods: The genotypes of l2 2 COPD patients and 100 controls with normal lung function were determined for CYP1A1 *1A /*2A , CYP2E1 *1 A /*5B , GSTM1 null, GSTT1 null GSTP1 Ile105Val, mEH Tyr113His and mEH His139Arg gene variants. Results: Results obtained showed that GSTM1 null variant was significantly more represented in COPD patients than in controls (61.5% vs. 47.0%; or = 1.80; p = 0.042). Also, a significant difference was observed for combinations of GSTM1 null and GSTP1 105Val/(Val) (38.5% vs. 24.0%; or = 1.98; p = 0.029), as well as for CYP1A1 *1A/*2A, GSTM1 null and mEH 113His/(His) genotypes (7.4% vs. 1.0%; or = 7.88; p = 0.025). Conclusions: These are the first data concerning the analysis of the variants of phase I and II genes in the pathogenesis of COPD in a Serbian population. Results obtained in this study open up the possibility for thorough analyses of the role of genetic factors in COPD on larger cohorts. Also, they implicate the importance of previously described genetic associations with COPD in our population, as well as reveal a new one, not reported so far.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Udruženost funkcionalnih varijanti gena faze I I II sa hroničnom opstruktivnom bolešću pluća u srpskoj populaciji, Association of functional variants of phase I and II genes with chronic obstructive pulmonary disease in a Serbian population",
pages = "214-207",
number = "2",
volume = "34",
doi = "10.2478/jomb-2014-0024"
}

Stanković, M., Nikolić, A., Tomović, A., Mitić-Milikić, M., Nagorni-Obradović, L., Petrović-Stanojević, N.,& Radojković, D.. (2015). Udruženost funkcionalnih varijanti gena faze I I II sa hroničnom opstruktivnom bolešću pluća u srpskoj populaciji. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 34(2), 207-214.
https://doi.org/10.2478/jomb-2014-0024

Stanković M, Nikolić A, Tomović A, Mitić-Milikić M, Nagorni-Obradović L, Petrović-Stanojević N, Radojković D. Udruženost funkcionalnih varijanti gena faze I I II sa hroničnom opstruktivnom bolešću pluća u srpskoj populaciji. in Journal of Medical Biochemistry. 2015;34(2):207-214.
doi:10.2478/jomb-2014-0024 .

Stanković, Marija, Nikolić, Aleksandra, Tomović, Andrija, Mitić-Milikić, Marija, Nagorni-Obradović, Ljudmila, Petrović-Stanojević, Nataša, Radojković, Dragica, "Udruženost funkcionalnih varijanti gena faze I I II sa hroničnom opstruktivnom bolešću pluća u srpskoj populaciji" in Journal of Medical Biochemistry, 34, no. 2 (2015):207-214,
https://doi.org/10.2478/jomb-2014-0024 . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Stanković, Marija
AU  - Divac Rankov, Aleksandra
AU  - Petrović-Stanojević, Nataša
AU  - Mitić-Milikić, Marija
AU  - Nagorni-Obradović, Ljudmila
AU  - Radojković, Dragica
PY  - 2012
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/595
AB  - Aim: Alpha-1-antitrypsin (A1AT) is the main inhibitor of neutrophil elastase, and severe alpha-1-antitrypsin deficiency (A1ATD) is a genetic risk factor for early-onset emphysema. Despite the relatively high prevalence of A1ATD, this condition is frequently underdiagnosed. Our aim was to determine the distribution of the A1ATD phenotypes/alleles in patients with lung diseases as well as in the Serbian population. Methods: The study included the adults with chronic obstructive pulmonary disease (COPD) (n = 348), asthma (n = 71), and bronchiectasis (n = 35); the control was 1435 healthy blood donors. The A1ATD variants were identified by isoelectric focusing or polymerase chain reaction-mediated site-directed mutagenesis. Results: PiMZ heterozygotes, PiZZ homozygotes, and Z allele carriers are associated with significantly higher risk of developing COPD than healthy individuals (odds ratios 3.43, 42.42, and 5.49 respectively). The calculated prevalence of PiZZ, PiMZ, and PiSZ was higher in patients with COPD (1:202, 1:8, and 1:1243) than in the Serbian population (1: 5519, 1: 38, and 1:5519). Conclusion: The high prevalence of A1ATD phenotypes/allele in our population has confirmed the necessity of screening for A1ATD in patients with COPD. On the other hand, on the basis of the estimated number of those with A1ATD among the COPD patients, it is possible to assess the diagnostic efficiency of A1ATD in the Serbian population.
PB  - Mary Ann Liebert, Inc, New Rochelle
T2  - Genetic Testing and Molecular Biomarkers
T1  - Alpha-1-Antitrypsin Deficiency in Serbian Adults with Lung Diseases
EP  - 1286
IS  - 11
SP  - 1282
VL  - 16
DO  - 10.1089/gtmb.2012.0152
ER  - 

@article{
author = "Topić, Aleksandra and Stanković, Marija and Divac Rankov, Aleksandra and Petrović-Stanojević, Nataša and Mitić-Milikić, Marija and Nagorni-Obradović, Ljudmila and Radojković, Dragica",
year = "2012",
abstract = "Aim: Alpha-1-antitrypsin (A1AT) is the main inhibitor of neutrophil elastase, and severe alpha-1-antitrypsin deficiency (A1ATD) is a genetic risk factor for early-onset emphysema. Despite the relatively high prevalence of A1ATD, this condition is frequently underdiagnosed. Our aim was to determine the distribution of the A1ATD phenotypes/alleles in patients with lung diseases as well as in the Serbian population. Methods: The study included the adults with chronic obstructive pulmonary disease (COPD) (n = 348), asthma (n = 71), and bronchiectasis (n = 35); the control was 1435 healthy blood donors. The A1ATD variants were identified by isoelectric focusing or polymerase chain reaction-mediated site-directed mutagenesis. Results: PiMZ heterozygotes, PiZZ homozygotes, and Z allele carriers are associated with significantly higher risk of developing COPD than healthy individuals (odds ratios 3.43, 42.42, and 5.49 respectively). The calculated prevalence of PiZZ, PiMZ, and PiSZ was higher in patients with COPD (1:202, 1:8, and 1:1243) than in the Serbian population (1: 5519, 1: 38, and 1:5519). Conclusion: The high prevalence of A1ATD phenotypes/allele in our population has confirmed the necessity of screening for A1ATD in patients with COPD. On the other hand, on the basis of the estimated number of those with A1ATD among the COPD patients, it is possible to assess the diagnostic efficiency of A1ATD in the Serbian population.",
publisher = "Mary Ann Liebert, Inc, New Rochelle",
journal = "Genetic Testing and Molecular Biomarkers",
title = "Alpha-1-Antitrypsin Deficiency in Serbian Adults with Lung Diseases",
pages = "1286-1282",
number = "11",
volume = "16",
doi = "10.1089/gtmb.2012.0152"
}

Topić, A., Stanković, M., Divac Rankov, A., Petrović-Stanojević, N., Mitić-Milikić, M., Nagorni-Obradović, L.,& Radojković, D.. (2012). Alpha-1-Antitrypsin Deficiency in Serbian Adults with Lung Diseases. in Genetic Testing and Molecular Biomarkers
Mary Ann Liebert, Inc, New Rochelle., 16(11), 1282-1286.
https://doi.org/10.1089/gtmb.2012.0152

Topić A, Stanković M, Divac Rankov A, Petrović-Stanojević N, Mitić-Milikić M, Nagorni-Obradović L, Radojković D. Alpha-1-Antitrypsin Deficiency in Serbian Adults with Lung Diseases. in Genetic Testing and Molecular Biomarkers. 2012;16(11):1282-1286.
doi:10.1089/gtmb.2012.0152 .

Topić, Aleksandra, Stanković, Marija, Divac Rankov, Aleksandra, Petrović-Stanojević, Nataša, Mitić-Milikić, Marija, Nagorni-Obradović, Ljudmila, Radojković, Dragica, "Alpha-1-Antitrypsin Deficiency in Serbian Adults with Lung Diseases" in Genetic Testing and Molecular Biomarkers, 16, no. 11 (2012):1282-1286,
https://doi.org/10.1089/gtmb.2012.0152 . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Ljujić, Mila
AU  - Nikolić, Aleksandra
AU  - Petrović-Stanojević, Nataša
AU  - Dopudja-Pantić, Vesna
AU  - Mitić-Milikić, Marija
AU  - Radojković, Dragica
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/508
AB  - Imbalance between neutrophil elastase and alpha-1-antitrypsin (AAT) leads to emphysema in smokers as well as in patients with inherited alpha-1-antitrypsin deficiency. AAT as a proven inhibitor of apoptosis may play role in lung cancer (LC) progression. The aim was to analyse AAT protein variants and polymorphism in promoter region of the neutrophil elastase gene (ELA2) in patients with primary lung cancer. AAT phenotypisation by isoelectric focusing method and ELA2 gene promoter characterization by DNA sequencing were performed in 66 patients with primary lung cancer. Results showed that the frequency of M1 allele and PiM1 homozygotes in LC patients was significantly higher when compared to the healthy subjects (f = 0.6360 and 0.7424 respectively). The most frequent ELA2 promoter region genotypes in LC patients were -903TT and -741GG. There were significantly more patients with intermediate and high ELA2 genotype activity, compared to those with low activity (91% vs. 9%, respectively). In conclusion, we found that PiM1 homozygosity could be associated with the lung cancer, probably due to increased synthesis of this antiapoptotic protein. Non-MM variants of AAT and ELA2 genotypes with predicted intermediate or high activity could also represent a risk factor for aggressive form of lung cancer associated with extrathoracic metastases.
PB  - Frontiers Media Sa, Lausanne
T2  - Pathology & Oncology Research
T1  - Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer
EP  - 80
IS  - 1
SP  - 75
VL  - 17
DO  - 10.1007/s12253-010-9283-5
ER  - 

@article{
author = "Topić, Aleksandra and Ljujić, Mila and Nikolić, Aleksandra and Petrović-Stanojević, Nataša and Dopudja-Pantić, Vesna and Mitić-Milikić, Marija and Radojković, Dragica",
year = "2011",
abstract = "Imbalance between neutrophil elastase and alpha-1-antitrypsin (AAT) leads to emphysema in smokers as well as in patients with inherited alpha-1-antitrypsin deficiency. AAT as a proven inhibitor of apoptosis may play role in lung cancer (LC) progression. The aim was to analyse AAT protein variants and polymorphism in promoter region of the neutrophil elastase gene (ELA2) in patients with primary lung cancer. AAT phenotypisation by isoelectric focusing method and ELA2 gene promoter characterization by DNA sequencing were performed in 66 patients with primary lung cancer. Results showed that the frequency of M1 allele and PiM1 homozygotes in LC patients was significantly higher when compared to the healthy subjects (f = 0.6360 and 0.7424 respectively). The most frequent ELA2 promoter region genotypes in LC patients were -903TT and -741GG. There were significantly more patients with intermediate and high ELA2 genotype activity, compared to those with low activity (91% vs. 9%, respectively). In conclusion, we found that PiM1 homozygosity could be associated with the lung cancer, probably due to increased synthesis of this antiapoptotic protein. Non-MM variants of AAT and ELA2 genotypes with predicted intermediate or high activity could also represent a risk factor for aggressive form of lung cancer associated with extrathoracic metastases.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Pathology & Oncology Research",
title = "Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer",
pages = "80-75",
number = "1",
volume = "17",
doi = "10.1007/s12253-010-9283-5"
}

Topić, A., Ljujić, M., Nikolić, A., Petrović-Stanojević, N., Dopudja-Pantić, V., Mitić-Milikić, M.,& Radojković, D.. (2011). Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer. in Pathology & Oncology Research
Frontiers Media Sa, Lausanne., 17(1), 75-80.
https://doi.org/10.1007/s12253-010-9283-5

Topić A, Ljujić M, Nikolić A, Petrović-Stanojević N, Dopudja-Pantić V, Mitić-Milikić M, Radojković D. Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer. in Pathology & Oncology Research. 2011;17(1):75-80.
doi:10.1007/s12253-010-9283-5 .

Topić, Aleksandra, Ljujić, Mila, Nikolić, Aleksandra, Petrović-Stanojević, Nataša, Dopudja-Pantić, Vesna, Mitić-Milikić, Marija, Radojković, Dragica, "Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer" in Pathology & Oncology Research, 17, no. 1 (2011):75-80,
https://doi.org/10.1007/s12253-010-9283-5 . .

TY  - JOUR
AU  - Ljujić, Mila
AU  - Topić, Aleksandra
AU  - Nikolić, Aleksandra
AU  - Divac Rankov, Aleksandra
AU  - Grujić, Milan
AU  - Mitić-Milikić, Marija
AU  - Radojković, Dragica
PY  - 2010
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/416
AB  - The alpha-1-antitrypsin (A1AT) gene is highly polymorphic, with more than 100 genetic variants identified of which some can affect A1AT protein concentration and/or function and lead to pulmonary and/or liver disease. This study reports on the characterization of a p.G320R variant found in two patients, one with emphysema and the other with lung cancer. This variant results from a single base-pair substitution in exon 4 of the A1AT gene, and has been characterized as P by isoelectric focusing. Functional evaluation of the A1AT p.G320R variant was through comparing specific trypsin inhibitory activity in two patients with pulmonary disorders, carriers of the p.G320R variant, and 19 healthy individuals, carriers of normal A1AT M variants. Results showed that specific trypsin inhibitory activity was lower in both emphysema (2.45 mU/g) and lung cancer (2.07 mU/g) patients than in carriers of the normal variants (range 2.51-3.71 mU/g). This rare A1AT variant is associated with reduced functional activity of A1AT protein. Considering that it was found in patients with severe pulmonary disorders, this variant could be of clinical significance.
PB  - Soc Brasil Genetica, Ribeirao Pret
T2  - Genetics and Molecular Biology
T1  - Identification of a rare p.G320R alpha-1-antitrypsin variant in emphysema and lung cancer patients
EP  - 8
IS  - 1
SP  - 5
VL  - 33
DO  - 10.1590/S1415-47572009005000100
ER  - 

@article{
author = "Ljujić, Mila and Topić, Aleksandra and Nikolić, Aleksandra and Divac Rankov, Aleksandra and Grujić, Milan and Mitić-Milikić, Marija and Radojković, Dragica",
year = "2010",
abstract = "The alpha-1-antitrypsin (A1AT) gene is highly polymorphic, with more than 100 genetic variants identified of which some can affect A1AT protein concentration and/or function and lead to pulmonary and/or liver disease. This study reports on the characterization of a p.G320R variant found in two patients, one with emphysema and the other with lung cancer. This variant results from a single base-pair substitution in exon 4 of the A1AT gene, and has been characterized as P by isoelectric focusing. Functional evaluation of the A1AT p.G320R variant was through comparing specific trypsin inhibitory activity in two patients with pulmonary disorders, carriers of the p.G320R variant, and 19 healthy individuals, carriers of normal A1AT M variants. Results showed that specific trypsin inhibitory activity was lower in both emphysema (2.45 mU/g) and lung cancer (2.07 mU/g) patients than in carriers of the normal variants (range 2.51-3.71 mU/g). This rare A1AT variant is associated with reduced functional activity of A1AT protein. Considering that it was found in patients with severe pulmonary disorders, this variant could be of clinical significance.",
publisher = "Soc Brasil Genetica, Ribeirao Pret",
journal = "Genetics and Molecular Biology",
title = "Identification of a rare p.G320R alpha-1-antitrypsin variant in emphysema and lung cancer patients",
pages = "8-5",
number = "1",
volume = "33",
doi = "10.1590/S1415-47572009005000100"
}

Ljujić, M., Topić, A., Nikolić, A., Divac Rankov, A., Grujić, M., Mitić-Milikić, M.,& Radojković, D.. (2010). Identification of a rare p.G320R alpha-1-antitrypsin variant in emphysema and lung cancer patients. in Genetics and Molecular Biology
Soc Brasil Genetica, Ribeirao Pret., 33(1), 5-8.
https://doi.org/10.1590/S1415-47572009005000100

Ljujić M, Topić A, Nikolić A, Divac Rankov A, Grujić M, Mitić-Milikić M, Radojković D. Identification of a rare p.G320R alpha-1-antitrypsin variant in emphysema and lung cancer patients. in Genetics and Molecular Biology. 2010;33(1):5-8.
doi:10.1590/S1415-47572009005000100 .

Ljujić, Mila, Topić, Aleksandra, Nikolić, Aleksandra, Divac Rankov, Aleksandra, Grujić, Milan, Mitić-Milikić, Marija, Radojković, Dragica, "Identification of a rare p.G320R alpha-1-antitrypsin variant in emphysema and lung cancer patients" in Genetics and Molecular Biology, 33, no. 1 (2010):5-8,
https://doi.org/10.1590/S1415-47572009005000100 . .

TY  - JOUR
AU  - Stanković, Marija
AU  - Nikolić, Aleksandra
AU  - Divac Rankov, Aleksandra
AU  - Rakićević, Ljiljana
AU  - Tomović, Andrija
AU  - Mitić-Milikić, Marija
AU  - Nagorni-Obradović, Ljudmila
AU  - Grujić, Milan
AU  - Petrović-Stanojević, Nataša
AU  - Anđelić-Jelić, Marina
AU  - Dopudja-Pantić, Vesna
AU  - Radojković, Dragica
PY  - 2009
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/356
AB  - Background: The excess of matrix metalloproteinases (MMPs) might be associated with the airways destruction or dilatation in bronchiectasis. The functional promoter polymorphisms of MMPI and MMP9 genes, involved in the extracellular matrix remodeling, might increase the expression of MMPs leading to the development of bronchiectasis. Methods: Detection of MMP1 G-1607GG and MMP9 C-1562T gene variants was performed on 37 patients with idiopathic disseminated bronchiectasis and 102 control subjects. We also described a novel method for simple and rapid detection of MMP1 G-1607GG polymorphism. Results: The frequency of -1607GG allele was significantly higher in the group of patients than in control subjects (P = 0.014). The heterozygote genotype showed association with bronchiectasis (odds ratio, 5.3; 95% confidence intervals, 1.4-20.0). The association was even stronger in homozygotes for -1607GG allele (odds ration, 8.7; 95% confidence intervals, 1.9-41.0). The allelic and genotype frequencies of MMP9 C-1562T variant did not show significant differences between the groups. Conclusions: This is the first report concerning a role of MMP1 G-1607GG and MMP9 C-1562T variants in pathogenesis of idiopathic disseminated bronchiectasis. The results of our study revealed the association of -1607GG allele and the lack of association of MMP9 C-1562T variant with the disease.
PB  - BMJ Publishing Group
T2  - Journal of Investigative Medicine
T1  - Matrix Metalloproteinases Gene Variants in Idiopathic Disseminated Bronchiectasis
EP  - 503
IS  - 3
SP  - 500
VL  - 57
DO  - 10.2310/JIM.0b013e318198277c
ER  - 

@article{
author = "Stanković, Marija and Nikolić, Aleksandra and Divac Rankov, Aleksandra and Rakićević, Ljiljana and Tomović, Andrija and Mitić-Milikić, Marija and Nagorni-Obradović, Ljudmila and Grujić, Milan and Petrović-Stanojević, Nataša and Anđelić-Jelić, Marina and Dopudja-Pantić, Vesna and Radojković, Dragica",
year = "2009",
abstract = "Background: The excess of matrix metalloproteinases (MMPs) might be associated with the airways destruction or dilatation in bronchiectasis. The functional promoter polymorphisms of MMPI and MMP9 genes, involved in the extracellular matrix remodeling, might increase the expression of MMPs leading to the development of bronchiectasis. Methods: Detection of MMP1 G-1607GG and MMP9 C-1562T gene variants was performed on 37 patients with idiopathic disseminated bronchiectasis and 102 control subjects. We also described a novel method for simple and rapid detection of MMP1 G-1607GG polymorphism. Results: The frequency of -1607GG allele was significantly higher in the group of patients than in control subjects (P = 0.014). The heterozygote genotype showed association with bronchiectasis (odds ratio, 5.3; 95% confidence intervals, 1.4-20.0). The association was even stronger in homozygotes for -1607GG allele (odds ration, 8.7; 95% confidence intervals, 1.9-41.0). The allelic and genotype frequencies of MMP9 C-1562T variant did not show significant differences between the groups. Conclusions: This is the first report concerning a role of MMP1 G-1607GG and MMP9 C-1562T variants in pathogenesis of idiopathic disseminated bronchiectasis. The results of our study revealed the association of -1607GG allele and the lack of association of MMP9 C-1562T variant with the disease.",
publisher = "BMJ Publishing Group",
journal = "Journal of Investigative Medicine",
title = "Matrix Metalloproteinases Gene Variants in Idiopathic Disseminated Bronchiectasis",
pages = "503-500",
number = "3",
volume = "57",
doi = "10.2310/JIM.0b013e318198277c"
}

Stanković, M., Nikolić, A., Divac Rankov, A., Rakićević, L., Tomović, A., Mitić-Milikić, M., Nagorni-Obradović, L., Grujić, M., Petrović-Stanojević, N., Anđelić-Jelić, M., Dopudja-Pantić, V.,& Radojković, D.. (2009). Matrix Metalloproteinases Gene Variants in Idiopathic Disseminated Bronchiectasis. in Journal of Investigative Medicine
BMJ Publishing Group., 57(3), 500-503.
https://doi.org/10.2310/JIM.0b013e318198277c

Stanković M, Nikolić A, Divac Rankov A, Rakićević L, Tomović A, Mitić-Milikić M, Nagorni-Obradović L, Grujić M, Petrović-Stanojević N, Anđelić-Jelić M, Dopudja-Pantić V, Radojković D. Matrix Metalloproteinases Gene Variants in Idiopathic Disseminated Bronchiectasis. in Journal of Investigative Medicine. 2009;57(3):500-503.
doi:10.2310/JIM.0b013e318198277c .

Stanković, Marija, Nikolić, Aleksandra, Divac Rankov, Aleksandra, Rakićević, Ljiljana, Tomović, Andrija, Mitić-Milikić, Marija, Nagorni-Obradović, Ljudmila, Grujić, Milan, Petrović-Stanojević, Nataša, Anđelić-Jelić, Marina, Dopudja-Pantić, Vesna, Radojković, Dragica, "Matrix Metalloproteinases Gene Variants in Idiopathic Disseminated Bronchiectasis" in Journal of Investigative Medicine, 57, no. 3 (2009):500-503,
https://doi.org/10.2310/JIM.0b013e318198277c . .

TY  - JOUR
AU  - Stanković, Marija
AU  - Nikolić, Aleksandra
AU  - Divac Rankov, Aleksandra
AU  - Tomović, Andrija
AU  - Petrović-Stanojević, Nataša
AU  - Anđelić, Marina
AU  - Dopudja-Pantić, Vesna
AU  - Surlan, Mirjana
AU  - Vujicić, Ivan
AU  - Ponomarev, Dimitrije
AU  - Mitić-Milikić, Marija
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica
PY  - 2008
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/316
AB  - Chronic obstructive pulmonary disease (COPD) is a complex disease influenced by genetic and environmental factors. Cystic fibrosis transmembrane conductance regulator (CFTR) protein is an important component of the lung tissue homeostasis, involved in the regulation of the rate of mucociliary clearance. As it is known that certain CFTR variants have consequences on the function of CFTR protein, the aim of this study was to examine the possible role of F508del, M470V, Tn locus, and R75Q variants in COPD development and modulation. Total number of 86 COPD patients and 102 control subjects were included in the study. Possible association between COPD susceptibility, severity, and onset of the disease and allele or genotype of four analyzed CFTR variants was examined. No associations were detected between COPD development, onset of the disease and tested CFTR alleles and genotypes. However, VV470 genotype was associated with mild/moderate COPD stages in comparison to severe/very severe ones (OR = 0.29, 95% CI = 0.11-0.80, p = 0.016). Our study showed that patients with VV470 genotype had a 3.4-fold decreased risk for the appearance of severe/very severe COPD symptoms, and the obtained results indicate that this genotype may have a protective role. These results also suggest the importance of studying CFTR gene as a modifier of this disease.
PB  - Mary Ann Liebert, Inc, New Rochelle
T2  - Genetic Testing
T1  - The CFTR M470V gene variant as a potential modifier of COPD severity: Study of Serbian population
EP  - 362
IS  - 3
SP  - 357
VL  - 12
DO  - 10.1089/gte.2007.0069
ER  - 

@article{
author = "Stanković, Marija and Nikolić, Aleksandra and Divac Rankov, Aleksandra and Tomović, Andrija and Petrović-Stanojević, Nataša and Anđelić, Marina and Dopudja-Pantić, Vesna and Surlan, Mirjana and Vujicić, Ivan and Ponomarev, Dimitrije and Mitić-Milikić, Marija and Kušić-Tišma, Jelena and Radojković, Dragica",
year = "2008",
abstract = "Chronic obstructive pulmonary disease (COPD) is a complex disease influenced by genetic and environmental factors. Cystic fibrosis transmembrane conductance regulator (CFTR) protein is an important component of the lung tissue homeostasis, involved in the regulation of the rate of mucociliary clearance. As it is known that certain CFTR variants have consequences on the function of CFTR protein, the aim of this study was to examine the possible role of F508del, M470V, Tn locus, and R75Q variants in COPD development and modulation. Total number of 86 COPD patients and 102 control subjects were included in the study. Possible association between COPD susceptibility, severity, and onset of the disease and allele or genotype of four analyzed CFTR variants was examined. No associations were detected between COPD development, onset of the disease and tested CFTR alleles and genotypes. However, VV470 genotype was associated with mild/moderate COPD stages in comparison to severe/very severe ones (OR = 0.29, 95% CI = 0.11-0.80, p = 0.016). Our study showed that patients with VV470 genotype had a 3.4-fold decreased risk for the appearance of severe/very severe COPD symptoms, and the obtained results indicate that this genotype may have a protective role. These results also suggest the importance of studying CFTR gene as a modifier of this disease.",
publisher = "Mary Ann Liebert, Inc, New Rochelle",
journal = "Genetic Testing",
title = "The CFTR M470V gene variant as a potential modifier of COPD severity: Study of Serbian population",
pages = "362-357",
number = "3",
volume = "12",
doi = "10.1089/gte.2007.0069"
}

Stanković, M., Nikolić, A., Divac Rankov, A., Tomović, A., Petrović-Stanojević, N., Anđelić, M., Dopudja-Pantić, V., Surlan, M., Vujicić, I., Ponomarev, D., Mitić-Milikić, M., Kušić-Tišma, J.,& Radojković, D.. (2008). The CFTR M470V gene variant as a potential modifier of COPD severity: Study of Serbian population. in Genetic Testing
Mary Ann Liebert, Inc, New Rochelle., 12(3), 357-362.
https://doi.org/10.1089/gte.2007.0069

Stanković M, Nikolić A, Divac Rankov A, Tomović A, Petrović-Stanojević N, Anđelić M, Dopudja-Pantić V, Surlan M, Vujicić I, Ponomarev D, Mitić-Milikić M, Kušić-Tišma J, Radojković D. The CFTR M470V gene variant as a potential modifier of COPD severity: Study of Serbian population. in Genetic Testing. 2008;12(3):357-362.
doi:10.1089/gte.2007.0069 .

Stanković, Marija, Nikolić, Aleksandra, Divac Rankov, Aleksandra, Tomović, Andrija, Petrović-Stanojević, Nataša, Anđelić, Marina, Dopudja-Pantić, Vesna, Surlan, Mirjana, Vujicić, Ivan, Ponomarev, Dimitrije, Mitić-Milikić, Marija, Kušić-Tišma, Jelena, Radojković, Dragica, "The CFTR M470V gene variant as a potential modifier of COPD severity: Study of Serbian population" in Genetic Testing, 12, no. 3 (2008):357-362,
https://doi.org/10.1089/gte.2007.0069 . .

TY  - JOUR
AU  - Nikolić, Aleksandra
AU  - Divac Rankov, Aleksandra
AU  - Bogdanović, Nada
AU  - Mitić-Milikić, Marija M.
AU  - Radojković, Dragica
PY  - 2004
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/200
AB  - U ovom radu je prikazan slučaj atipične cistične fibroze sa graničnom vrednošću znojnog testa. U većini slučajeva znojni test je glavni dijagnostički parametar za dijagnostikovanje cistične fibroze, ali se dijagnoza može potvrditi samo na osnovu rezultata molekularno-genetičkog testiranja. Utvrđeno je da je pacijent složeni heterozigot za dve CFTR mutacije, F508del i D1152H. Prisustvo mutacije F508del detektovano je PSM metodom, dok je za analizu prisustva druge mutacije korišćena DGGE metoda. Strategija detekcije mutacija kod pacijenata sa cističnom fibrozom, naročito onih sa atipičnim prezentacijama bolesti koji nose ređe mutacije, trebalo bi da uključuje i direktne i indirektne metode molekularne dijagnostike.
AB  - This paper reports a case of a patient presenting with atypical cystic fibrosis whose sweat test shows borderline values. In vast majority of cases the sweat test is essential diagnostic tool for establishing the diagnosis of cystic fibrosis, but only after the molecular genetic testing the diagnosis can be confirmed. The patient was found to be compound heterozygote for two CFTR mutations, F508del and D1152H. The presence of F508del mutation was analyzed by PSM method, while the screening for the second mutation was performed using DGGE. The strategy of mutation detection in cystic fibrosis patients, especially those with atypical presentations who carry less frequent mutations, should include both direct and indirect methods of molecular diagnostics.
PB  - Društvo medicinskih biohemičara Srbije i Crne Gore, Beograd i Univerzitet u Beogradu - Farmaceutski fakultet, Beograd
T2  - Jugoslovenska medicinska biohemija
T1  - Analiza CFTR gena kod pacijenta sa atipičnom cističnom fibrozom
T1  - CFTR gene analysis in patient with atypical cystic fibrosis
EP  - 354
IS  - 4
SP  - 351
VL  - 23
DO  - 10.2298/JMH0404351N
ER  - 

@article{
author = "Nikolić, Aleksandra and Divac Rankov, Aleksandra and Bogdanović, Nada and Mitić-Milikić, Marija M. and Radojković, Dragica",
year = "2004",
abstract = "U ovom radu je prikazan slučaj atipične cistične fibroze sa graničnom vrednošću znojnog testa. U većini slučajeva znojni test je glavni dijagnostički parametar za dijagnostikovanje cistične fibroze, ali se dijagnoza može potvrditi samo na osnovu rezultata molekularno-genetičkog testiranja. Utvrđeno je da je pacijent složeni heterozigot za dve CFTR mutacije, F508del i D1152H. Prisustvo mutacije F508del detektovano je PSM metodom, dok je za analizu prisustva druge mutacije korišćena DGGE metoda. Strategija detekcije mutacija kod pacijenata sa cističnom fibrozom, naročito onih sa atipičnim prezentacijama bolesti koji nose ređe mutacije, trebalo bi da uključuje i direktne i indirektne metode molekularne dijagnostike., This paper reports a case of a patient presenting with atypical cystic fibrosis whose sweat test shows borderline values. In vast majority of cases the sweat test is essential diagnostic tool for establishing the diagnosis of cystic fibrosis, but only after the molecular genetic testing the diagnosis can be confirmed. The patient was found to be compound heterozygote for two CFTR mutations, F508del and D1152H. The presence of F508del mutation was analyzed by PSM method, while the screening for the second mutation was performed using DGGE. The strategy of mutation detection in cystic fibrosis patients, especially those with atypical presentations who carry less frequent mutations, should include both direct and indirect methods of molecular diagnostics.",
publisher = "Društvo medicinskih biohemičara Srbije i Crne Gore, Beograd i Univerzitet u Beogradu - Farmaceutski fakultet, Beograd",
journal = "Jugoslovenska medicinska biohemija",
title = "Analiza CFTR gena kod pacijenta sa atipičnom cističnom fibrozom, CFTR gene analysis in patient with atypical cystic fibrosis",
pages = "354-351",
number = "4",
volume = "23",
doi = "10.2298/JMH0404351N"
}

Nikolić, A., Divac Rankov, A., Bogdanović, N., Mitić-Milikić, M. M.,& Radojković, D.. (2004). Analiza CFTR gena kod pacijenta sa atipičnom cističnom fibrozom. in Jugoslovenska medicinska biohemija
Društvo medicinskih biohemičara Srbije i Crne Gore, Beograd i Univerzitet u Beogradu - Farmaceutski fakultet, Beograd., 23(4), 351-354.
https://doi.org/10.2298/JMH0404351N

Nikolić A, Divac Rankov A, Bogdanović N, Mitić-Milikić MM, Radojković D. Analiza CFTR gena kod pacijenta sa atipičnom cističnom fibrozom. in Jugoslovenska medicinska biohemija. 2004;23(4):351-354.
doi:10.2298/JMH0404351N .

Nikolić, Aleksandra, Divac Rankov, Aleksandra, Bogdanović, Nada, Mitić-Milikić, Marija M., Radojković, Dragica, "Analiza CFTR gena kod pacijenta sa atipičnom cističnom fibrozom" in Jugoslovenska medicinska biohemija, 23, no. 4 (2004):351-354,
https://doi.org/10.2298/JMH0404351N . .