TY  - JOUR
AU  - Malić, Zivka
AU  - Topić, Aleksandra
AU  - Francuski, Djordje
AU  - Stanković, Marija
AU  - Nagorni-Obradović, Ljudmila
AU  - Marković, Bojan
AU  - Radojković, Dragica
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1057
AB  - The genetic and non-genetic factors that contribute to the development of chronic obstructive pulmonary disease (COPD) are still poorly understood. We investigated the potential role of genetic variants of xenobiotic-metabolising enzymes (glutathione-S-transferase M1, GSTM1; glutathione-S-transferase T1, GSTT1; microsomal epoxide hydrolase, mEH), oxidative stress (assessed by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodG/creatinine), sex, ageing and smoking habits on susceptibility to development of COPD and its severity in Serbian population. The investigated population consisted of 153 healthy subjects (85 males and 68 females) and 71 patients with COPD (33 males and 38 females). Detection of GSTM1*null, GSTT1*null, mEH Tyr113His and mEH His139Arg gene variants was performed by PCR/RFLP method. Urinary 8-oxodG was determined using HPLC-MS/MS, and expressed as 8-oxodG/creatinine. We revealed that increased urinary 8-oxodG/creatinine and leucocytosis are the strongest independent predictors for COPD development. Increased level of oxidative stress increased the risk for COPD in males [odds ratio (OR), 95% confidence interval (CI): 8.42, 2.26-31.28], more than in females (OR, 95% CI: 3.60, 1.37-9.45). Additionally, independent predictors for COPD were ageing in males (OR, 95% CI: 1.29, 1.12-1.48), while in females they were at least one GSTM1 or GSTT1 gene deletion in combination (OR, 95% CI: 23.67, 2.62-213.46), and increased cumulative cigarette consumption (OR, 95% CI: 1.09, 1.01-1.16). Severity of COPD was associated with the combined effect of low mEH activity phenotype, high level of oxidative stress and heavy smoking. In conclusion, early identification of GSTM1*null or GSTT1*null genotypes in females, low mEH activity phenotype in heavy smokers and monitoring of oxidative stress level can be useful diagnostic and prognostic biomarkers.
PB  - Taylor & Francis Inc, Philadelphia
T2  - COPD-Journal of Chronic Obstructive Pulmonary Disease
T1  - Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults
EP  - 104
IS  - 1
SP  - 95
VL  - 14
DO  - 10.1080/15412555.2016.1199667
ER  - 

@article{
author = "Malić, Zivka and Topić, Aleksandra and Francuski, Djordje and Stanković, Marija and Nagorni-Obradović, Ljudmila and Marković, Bojan and Radojković, Dragica",
year = "2017",
abstract = "The genetic and non-genetic factors that contribute to the development of chronic obstructive pulmonary disease (COPD) are still poorly understood. We investigated the potential role of genetic variants of xenobiotic-metabolising enzymes (glutathione-S-transferase M1, GSTM1; glutathione-S-transferase T1, GSTT1; microsomal epoxide hydrolase, mEH), oxidative stress (assessed by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodG/creatinine), sex, ageing and smoking habits on susceptibility to development of COPD and its severity in Serbian population. The investigated population consisted of 153 healthy subjects (85 males and 68 females) and 71 patients with COPD (33 males and 38 females). Detection of GSTM1*null, GSTT1*null, mEH Tyr113His and mEH His139Arg gene variants was performed by PCR/RFLP method. Urinary 8-oxodG was determined using HPLC-MS/MS, and expressed as 8-oxodG/creatinine. We revealed that increased urinary 8-oxodG/creatinine and leucocytosis are the strongest independent predictors for COPD development. Increased level of oxidative stress increased the risk for COPD in males [odds ratio (OR), 95% confidence interval (CI): 8.42, 2.26-31.28], more than in females (OR, 95% CI: 3.60, 1.37-9.45). Additionally, independent predictors for COPD were ageing in males (OR, 95% CI: 1.29, 1.12-1.48), while in females they were at least one GSTM1 or GSTT1 gene deletion in combination (OR, 95% CI: 23.67, 2.62-213.46), and increased cumulative cigarette consumption (OR, 95% CI: 1.09, 1.01-1.16). Severity of COPD was associated with the combined effect of low mEH activity phenotype, high level of oxidative stress and heavy smoking. In conclusion, early identification of GSTM1*null or GSTT1*null genotypes in females, low mEH activity phenotype in heavy smokers and monitoring of oxidative stress level can be useful diagnostic and prognostic biomarkers.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "COPD-Journal of Chronic Obstructive Pulmonary Disease",
title = "Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults",
pages = "104-95",
number = "1",
volume = "14",
doi = "10.1080/15412555.2016.1199667"
}

Malić, Z., Topić, A., Francuski, D., Stanković, M., Nagorni-Obradović, L., Marković, B.,& Radojković, D.. (2017). Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults. in COPD-Journal of Chronic Obstructive Pulmonary Disease
Taylor & Francis Inc, Philadelphia., 14(1), 95-104.
https://doi.org/10.1080/15412555.2016.1199667

Malić Z, Topić A, Francuski D, Stanković M, Nagorni-Obradović L, Marković B, Radojković D. Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults. in COPD-Journal of Chronic Obstructive Pulmonary Disease. 2017;14(1):95-104.
doi:10.1080/15412555.2016.1199667 .

Malić, Zivka, Topić, Aleksandra, Francuski, Djordje, Stanković, Marija, Nagorni-Obradović, Ljudmila, Marković, Bojan, Radojković, Dragica, "Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults" in COPD-Journal of Chronic Obstructive Pulmonary Disease, 14, no. 1 (2017):95-104,
https://doi.org/10.1080/15412555.2016.1199667 . .

TY  - JOUR
AU  - Stanković, Marija
AU  - Nikolić, Aleksandra
AU  - Nagorni-Obradović, Ljudmila
AU  - Petrović-Stanojević, Nataša
AU  - Radojković, Dragica
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1032
AB  - Chronic obstructive pulmonary disease (COPD) is a complex disorder influenced by multiple genetic and environmental factors, as well as their interactions. Since elevated oxidative stress and protease activity characterize the pathogenesis of COPD, variants of genes that can affect these processes have been commonly studied in COPD. However, interactions among genes that can influence oxidative stress and protease activity remain poorly investigated in COPD. The aim of this study was to look into the role of functional variants in matrix metalloproteinases (MMPs) 1, 9, and 12 in the occurrence and/or modulation of COPD, and to analyze their interactions with glutathione S-transferases (GSTs) M1, T1, and P1 in the pathogenesis of COPD in Serbians. The MMP1 rs1799750 G  gt  GG, MMP9 rs3918242 C  gt  T, and MMP12 rs2276109 A  gt  G variants were analyzed by direct detection methods. Gene-gene interactions between variants in MMPs and GSTs were assessed using a case-control model. Our results showed association of the MMP1 GG/GG genotype with COPD (p = 0.036, OR = 2.50). Gene-gene interactions between the GSTM1 null and MMP1 GG (p = 0.028, OR = 2.99) and the GSTM1 null and MMP12 AA variants (p = 0.015, OR = 3.82) were found to significantly increase the risk of COPD occurrence. Furthermore, the MMP12 G variant was found to modify the age of COPD onset (p = 0.025, OR = 3.30), while interaction between the GSTM1 null and MMP9 T variants was found to modify the severity of disease (p = 0.019, OR = 4.83). To our best knowledge, this is the first study revealing several gene-gene interactions affecting oxidative stress and protease activity in the pathogenesis of COPD.
PB  - Taylor & Francis Inc, Philadelphia
T2  - COPD-Journal of Chronic Obstructive Pulmonary Disease
T1  - Gene-Gene Interactions Between Glutathione S-Transferase M1 and Matrix Metalloproteinases 1, 9, and 12 in Chronic Obstructive Pulmonary Disease in Serbians
EP  - 589
IS  - 6
SP  - 581
VL  - 14
DO  - 10.1080/15412555.2017.1369022
ER  - 

@article{
author = "Stanković, Marija and Nikolić, Aleksandra and Nagorni-Obradović, Ljudmila and Petrović-Stanojević, Nataša and Radojković, Dragica",
year = "2017",
abstract = "Chronic obstructive pulmonary disease (COPD) is a complex disorder influenced by multiple genetic and environmental factors, as well as their interactions. Since elevated oxidative stress and protease activity characterize the pathogenesis of COPD, variants of genes that can affect these processes have been commonly studied in COPD. However, interactions among genes that can influence oxidative stress and protease activity remain poorly investigated in COPD. The aim of this study was to look into the role of functional variants in matrix metalloproteinases (MMPs) 1, 9, and 12 in the occurrence and/or modulation of COPD, and to analyze their interactions with glutathione S-transferases (GSTs) M1, T1, and P1 in the pathogenesis of COPD in Serbians. The MMP1 rs1799750 G  gt  GG, MMP9 rs3918242 C  gt  T, and MMP12 rs2276109 A  gt  G variants were analyzed by direct detection methods. Gene-gene interactions between variants in MMPs and GSTs were assessed using a case-control model. Our results showed association of the MMP1 GG/GG genotype with COPD (p = 0.036, OR = 2.50). Gene-gene interactions between the GSTM1 null and MMP1 GG (p = 0.028, OR = 2.99) and the GSTM1 null and MMP12 AA variants (p = 0.015, OR = 3.82) were found to significantly increase the risk of COPD occurrence. Furthermore, the MMP12 G variant was found to modify the age of COPD onset (p = 0.025, OR = 3.30), while interaction between the GSTM1 null and MMP9 T variants was found to modify the severity of disease (p = 0.019, OR = 4.83). To our best knowledge, this is the first study revealing several gene-gene interactions affecting oxidative stress and protease activity in the pathogenesis of COPD.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "COPD-Journal of Chronic Obstructive Pulmonary Disease",
title = "Gene-Gene Interactions Between Glutathione S-Transferase M1 and Matrix Metalloproteinases 1, 9, and 12 in Chronic Obstructive Pulmonary Disease in Serbians",
pages = "589-581",
number = "6",
volume = "14",
doi = "10.1080/15412555.2017.1369022"
}

Stanković, M., Nikolić, A., Nagorni-Obradović, L., Petrović-Stanojević, N.,& Radojković, D.. (2017). Gene-Gene Interactions Between Glutathione S-Transferase M1 and Matrix Metalloproteinases 1, 9, and 12 in Chronic Obstructive Pulmonary Disease in Serbians. in COPD-Journal of Chronic Obstructive Pulmonary Disease
Taylor & Francis Inc, Philadelphia., 14(6), 581-589.
https://doi.org/10.1080/15412555.2017.1369022

Stanković M, Nikolić A, Nagorni-Obradović L, Petrović-Stanojević N, Radojković D. Gene-Gene Interactions Between Glutathione S-Transferase M1 and Matrix Metalloproteinases 1, 9, and 12 in Chronic Obstructive Pulmonary Disease in Serbians. in COPD-Journal of Chronic Obstructive Pulmonary Disease. 2017;14(6):581-589.
doi:10.1080/15412555.2017.1369022 .

Stanković, Marija, Nikolić, Aleksandra, Nagorni-Obradović, Ljudmila, Petrović-Stanojević, Nataša, Radojković, Dragica, "Gene-Gene Interactions Between Glutathione S-Transferase M1 and Matrix Metalloproteinases 1, 9, and 12 in Chronic Obstructive Pulmonary Disease in Serbians" in COPD-Journal of Chronic Obstructive Pulmonary Disease, 14, no. 6 (2017):581-589,
https://doi.org/10.1080/15412555.2017.1369022 . .

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  - Topić, Aleksandra
AU  - Nagorni-Obradović, Ljudmila
AU  - Francuski, Djordje
AU  - Ljujić, Mila
AU  - Malić, Zivka
AU  - Radojković, Dragica
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/900
AB  - Alpha-1-antitrypsin deficiency (AATD) and tobacco smoke play a key role in the pathogenesis of early-onset emphysema. Differences in AATD-related chronic obstructive pulmonary disease stages imply the existence of modifying factors associated with disease severity. We present two male patients with emphysema caused by severe AATD (PiZZ genotype). Both are former smokers and have epoxide hydrolase low-activity phenotype. Extremely high level of oxidative stress (high urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine), increased inflammation (high serum CRP), and GSTP1 105Val mutation were found in patient with a worse lung function and prognosis. These data provide more evidence that oxidative stress-related gene variants and inflammation are associated with worse symptoms of AATD-related emphysema. Therefore, prevention against severe stage of AATD-related emphysema would include early identification of the risk gene variants, cessation or never smoking, and treatment with anti-inflammatory and anti-oxidant drugs. Additionally, urinary 8-oxodG could be a candidate for predictive biomarker for routine assessment of the oxidative stress level in AATD patients.
PB  - Springer/Plenum Publishers, New York
T2  - Biochemical Genetics
T1  - Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency
EP  - 752
IS  - 5
SP  - 746
VL  - 54
DO  - 10.1007/s10528-016-9748-7
ER  - 

@article{
author = "Topić, Aleksandra and Nagorni-Obradović, Ljudmila and Francuski, Djordje and Ljujić, Mila and Malić, Zivka and Radojković, Dragica",
year = "2016",
abstract = "Alpha-1-antitrypsin deficiency (AATD) and tobacco smoke play a key role in the pathogenesis of early-onset emphysema. Differences in AATD-related chronic obstructive pulmonary disease stages imply the existence of modifying factors associated with disease severity. We present two male patients with emphysema caused by severe AATD (PiZZ genotype). Both are former smokers and have epoxide hydrolase low-activity phenotype. Extremely high level of oxidative stress (high urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine), increased inflammation (high serum CRP), and GSTP1 105Val mutation were found in patient with a worse lung function and prognosis. These data provide more evidence that oxidative stress-related gene variants and inflammation are associated with worse symptoms of AATD-related emphysema. Therefore, prevention against severe stage of AATD-related emphysema would include early identification of the risk gene variants, cessation or never smoking, and treatment with anti-inflammatory and anti-oxidant drugs. Additionally, urinary 8-oxodG could be a candidate for predictive biomarker for routine assessment of the oxidative stress level in AATD patients.",
publisher = "Springer/Plenum Publishers, New York",
journal = "Biochemical Genetics",
title = "Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency",
pages = "752-746",
number = "5",
volume = "54",
doi = "10.1007/s10528-016-9748-7"
}

Topić, A., Nagorni-Obradović, L., Francuski, D., Ljujić, M., Malić, Z.,& Radojković, D.. (2016). Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency. in Biochemical Genetics
Springer/Plenum Publishers, New York., 54(5), 746-752.
https://doi.org/10.1007/s10528-016-9748-7

Topić A, Nagorni-Obradović L, Francuski D, Ljujić M, Malić Z, Radojković D. Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency. in Biochemical Genetics. 2016;54(5):746-752.
doi:10.1007/s10528-016-9748-7 .

Topić, Aleksandra, Nagorni-Obradović, Ljudmila, Francuski, Djordje, Ljujić, Mila, Malić, Zivka, Radojković, Dragica, "Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency" in Biochemical Genetics, 54, no. 5 (2016):746-752,
https://doi.org/10.1007/s10528-016-9748-7 . .

TY  - JOUR
AU  - Beletić, Anđelo
AU  - Dudvarski-Ilić, Aleksandra
AU  - Milenković, Branislava
AU  - Nagorni-Obradović, Ljudmila
AU  - Ljujić, Mila
AU  - Đorđević, Valentina
AU  - Mirković, Dusko
AU  - Radojković, Dragica
AU  - Majkic-Singh, Nada
PY  - 2014
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/715
AB  - Introduction: Alpha-1-antitrypsin deficiency (AATD), genetic risk factor for premature chronic obstructive pulmonary disease (COPD), often remains undetected. The aim of our study was to analyse the effectiveness of an integrative laboratory algorithm for AATD detection in patients diagnosed with COPD by the age of 45 years, in comparison with the screening approach based on AAT concentration measurement alone. Subjects and methods: 50 unrelated patients (28 males / 22 females, age 52 (24-75 years) diagnosed with COPD before the age of 45 years were enrolled. Immunonephelometric assay for alpha-1-antitrypsin (AAT) and PCR-reverse hybridization for Z and S allele were first-line, and isoelectric focusing and DNA sequencing (ABI Prism BigDye) were reflex tests. Results: AATD associated genotypes were detected in 7 patients (5 ZZ, 1 ZM(malton), 1 ZQ0(amersfoort)), 10 were heterozygous carriers (8 MZ and 2 MS genotypes) and 33 were without AATD (MM genotype). Carriers and patients without AATD had comparable AAT concentrations (P = 0.125). In majority of participants (48) first line tests were sufficient to analyze AATD presence. In two remaining cases reflex tests identified rare alleles, M-malton and Q0(amersfoort), the later one being reported for the first time in Serbian population. Detection rate did not differ between algorithm and screening both for AATD (P = 0.500) and carriers (P = 0.063). Conclusion: There is a high prevalence of AATD affected subjects and carriers in a group of patients with premature COPD. The use of integrative laboratory algorithm does not improve the effectiveness of AATD detection in comparison with the screening based on AAT concentration alone.
PB  - Croatian Soc Medical Biochemists, Zagreb
T2  - Biochemia Medica
T1  - Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?
EP  - 298
IS  - 2
SP  - 293
VL  - 24
DO  - 10.11613/BM.2014.032
ER  - 

@article{
author = "Beletić, Anđelo and Dudvarski-Ilić, Aleksandra and Milenković, Branislava and Nagorni-Obradović, Ljudmila and Ljujić, Mila and Đorđević, Valentina and Mirković, Dusko and Radojković, Dragica and Majkic-Singh, Nada",
year = "2014",
abstract = "Introduction: Alpha-1-antitrypsin deficiency (AATD), genetic risk factor for premature chronic obstructive pulmonary disease (COPD), often remains undetected. The aim of our study was to analyse the effectiveness of an integrative laboratory algorithm for AATD detection in patients diagnosed with COPD by the age of 45 years, in comparison with the screening approach based on AAT concentration measurement alone. Subjects and methods: 50 unrelated patients (28 males / 22 females, age 52 (24-75 years) diagnosed with COPD before the age of 45 years were enrolled. Immunonephelometric assay for alpha-1-antitrypsin (AAT) and PCR-reverse hybridization for Z and S allele were first-line, and isoelectric focusing and DNA sequencing (ABI Prism BigDye) were reflex tests. Results: AATD associated genotypes were detected in 7 patients (5 ZZ, 1 ZM(malton), 1 ZQ0(amersfoort)), 10 were heterozygous carriers (8 MZ and 2 MS genotypes) and 33 were without AATD (MM genotype). Carriers and patients without AATD had comparable AAT concentrations (P = 0.125). In majority of participants (48) first line tests were sufficient to analyze AATD presence. In two remaining cases reflex tests identified rare alleles, M-malton and Q0(amersfoort), the later one being reported for the first time in Serbian population. Detection rate did not differ between algorithm and screening both for AATD (P = 0.500) and carriers (P = 0.063). Conclusion: There is a high prevalence of AATD affected subjects and carriers in a group of patients with premature COPD. The use of integrative laboratory algorithm does not improve the effectiveness of AATD detection in comparison with the screening based on AAT concentration alone.",
publisher = "Croatian Soc Medical Biochemists, Zagreb",
journal = "Biochemia Medica",
title = "Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?",
pages = "298-293",
number = "2",
volume = "24",
doi = "10.11613/BM.2014.032"
}

Beletić, A., Dudvarski-Ilić, A., Milenković, B., Nagorni-Obradović, L., Ljujić, M., Đorđević, V., Mirković, D., Radojković, D.,& Majkic-Singh, N.. (2014). Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?. in Biochemia Medica
Croatian Soc Medical Biochemists, Zagreb., 24(2), 293-298.
https://doi.org/10.11613/BM.2014.032

Beletić A, Dudvarski-Ilić A, Milenković B, Nagorni-Obradović L, Ljujić M, Đorđević V, Mirković D, Radojković D, Majkic-Singh N. Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?. in Biochemia Medica. 2014;24(2):293-298.
doi:10.11613/BM.2014.032 .

Beletić, Anđelo, Dudvarski-Ilić, Aleksandra, Milenković, Branislava, Nagorni-Obradović, Ljudmila, Ljujić, Mila, Đorđević, Valentina, Mirković, Dusko, Radojković, Dragica, Majkic-Singh, Nada, "Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?" in Biochemia Medica, 24, no. 2 (2014):293-298,
https://doi.org/10.11613/BM.2014.032 . .

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  - 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 . .