TY  - JOUR
AU  - Milovanovic, V.
AU  - Topic, A.
AU  - Milinkovic, N.
AU  - Lazic, Z.
AU  - Ivosevic, A.
AU  - Radojkovic, D.
AU  - Divac Rankov, Aleksandra
PY  - 2024
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1647
AB  - ObjectiveChronic obstructive pulmonary disease (COPD) is multi–factorial disorder which results from environmental influences and genetic factors. We aimed to investigate whether methionine sulfoxide reductase A (MSRA) rs10903323 gene polymorphism is associated with COPD development and severity in Serbian adult population.MethodsThe study included 155 patients with COPD and 134 healthy volunteers. Genotyping was determined performing home-made polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The difference between the inhibitory activities of normal and oxidized Alpha-1-Antitrypsin (A1AT) against elastase and trypsin was used for determination of Oxidized Alpha-1-Antitrypsin (OxyA1AT) (expressed as % and g/L). Functional activity of A1AT was presented as a specific inhibitor activity to elastase (SIA-Elastase, kU/g).ResultsFrequencies of the genotypes AA, AG and GG were 80.0%, 20.0%, 0% in COPD patients and 80.5%, 18.5% and 1.5% in the control group, and there was no significant difference in genotype or allele distributions between groups. Serum level of A1AT (g/L) and OxyA1AT was significantly higher in COPD patients than in the control group, but functional activity of A1AT (SIA-Elastase) was significantly lower in COPD patients than in the control group. In COPD group, increased level of OxyA1AT was present in G allele carriers who were smokers relative to G allele carriers who were not smokers. In the smoker group of patients with severe and very severe COPD (GOLD3+4), significant increase in OxyA1AT level was present in G allele carriers compared to AA homozygotes.ConclusionThese findings suggest that MSRA rs10903323 gene polymorphism is probably not a risk for COPD by itself but could represent a COPD modifier, since minor, G allele, is associated with an increased level of oxidized A1AT, indicating impaired ability of MSRA to repair oxidized A1AT in COPD-smokers, and in severe form of COPD.
PB  - Elsevier
T2  - Pulmonology
T2  - Pulmonology
T1  - Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients
EP  - 129
IS  - 2
SP  - 122
VL  - 30
DO  - 10.1016/j.pulmoe.2021.09.003
ER  - 

@article{
author = "Milovanovic, V. and Topic, A. and Milinkovic, N. and Lazic, Z. and Ivosevic, A. and Radojkovic, D. and Divac Rankov, Aleksandra",
year = "2024",
abstract = "ObjectiveChronic obstructive pulmonary disease (COPD) is multi–factorial disorder which results from environmental influences and genetic factors. We aimed to investigate whether methionine sulfoxide reductase A (MSRA) rs10903323 gene polymorphism is associated with COPD development and severity in Serbian adult population.MethodsThe study included 155 patients with COPD and 134 healthy volunteers. Genotyping was determined performing home-made polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The difference between the inhibitory activities of normal and oxidized Alpha-1-Antitrypsin (A1AT) against elastase and trypsin was used for determination of Oxidized Alpha-1-Antitrypsin (OxyA1AT) (expressed as % and g/L). Functional activity of A1AT was presented as a specific inhibitor activity to elastase (SIA-Elastase, kU/g).ResultsFrequencies of the genotypes AA, AG and GG were 80.0%, 20.0%, 0% in COPD patients and 80.5%, 18.5% and 1.5% in the control group, and there was no significant difference in genotype or allele distributions between groups. Serum level of A1AT (g/L) and OxyA1AT was significantly higher in COPD patients than in the control group, but functional activity of A1AT (SIA-Elastase) was significantly lower in COPD patients than in the control group. In COPD group, increased level of OxyA1AT was present in G allele carriers who were smokers relative to G allele carriers who were not smokers. In the smoker group of patients with severe and very severe COPD (GOLD3+4), significant increase in OxyA1AT level was present in G allele carriers compared to AA homozygotes.ConclusionThese findings suggest that MSRA rs10903323 gene polymorphism is probably not a risk for COPD by itself but could represent a COPD modifier, since minor, G allele, is associated with an increased level of oxidized A1AT, indicating impaired ability of MSRA to repair oxidized A1AT in COPD-smokers, and in severe form of COPD.",
publisher = "Elsevier",
journal = "Pulmonology, Pulmonology",
title = "Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients",
pages = "129-122",
number = "2",
volume = "30",
doi = "10.1016/j.pulmoe.2021.09.003"
}

Milovanovic, V., Topic, A., Milinkovic, N., Lazic, Z., Ivosevic, A., Radojkovic, D.,& Divac Rankov, A.. (2024). Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients. in Pulmonology
Elsevier., 30(2), 122-129.
https://doi.org/10.1016/j.pulmoe.2021.09.003

Milovanovic V, Topic A, Milinkovic N, Lazic Z, Ivosevic A, Radojkovic D, Divac Rankov A. Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients. in Pulmonology. 2024;30(2):122-129.
doi:10.1016/j.pulmoe.2021.09.003 .

Milovanovic, V., Topic, A., Milinkovic, N., Lazic, Z., Ivosevic, A., Radojkovic, D., Divac Rankov, Aleksandra, "Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients" in Pulmonology, 30, no. 2 (2024):122-129,
https://doi.org/10.1016/j.pulmoe.2021.09.003 . .