TY  - JOUR
AU  - Milovanović, Vera
AU  - Topić, Aleksandra
AU  - Milinković, Neda
AU  - Lazić, Zorica
AU  - Ivošević, Anita
AU  - Radojković, Dragica
AU  - Divac Rankov, Aleksandra
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4003
AB  - Objective: Chronic 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.
Methods: The 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 oxi-
dized Alpha-1-Antitrypsin (A1AT) against elastase and trypsin was used for determination of Oxi-
dized 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).
Results: Frequencies 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 geno-
type or allele distributions between groups. Serum level of A1AT (g/L) and OxyA1AT was signifi-
cantly 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 OxyA1ATwas 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.
Conclusion: These 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
T1  - Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients
VL  - 30
IS  - 2
SP  - 122
EP  - 129
DO  - 10.1016/j.pulmoe.2021.09.003
ER  - 

@article{
author = "Milovanović, Vera and Topić, Aleksandra and Milinković, Neda and Lazić, Zorica and Ivošević, Anita and Radojković, Dragica and Divac Rankov, Aleksandra",
year = "2024",
abstract = "Objective: Chronic 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.
Methods: The 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 oxi-
dized Alpha-1-Antitrypsin (A1AT) against elastase and trypsin was used for determination of Oxi-
dized 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).
Results: Frequencies 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 geno-
type or allele distributions between groups. Serum level of A1AT (g/L) and OxyA1AT was signifi-
cantly 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 OxyA1ATwas 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.
Conclusion: These 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",
title = "Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients",
volume = "30",
number = "2",
pages = "122-129",
doi = "10.1016/j.pulmoe.2021.09.003"
}

Milovanović, V., Topić, A., Milinković, N., Lazić, Z., Ivošević, A., Radojković, 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

Milovanović V, Topić A, Milinković N, Lazić Z, Ivošević A, Radojković 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 .

Milovanović, Vera, Topić, Aleksandra, Milinković, Neda, Lazić, Zorica, Ivošević, Anita, Radojković, Dragica, 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 . .