Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients.

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 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).

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 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.

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.

• Authors: V Milovanovic, A Topic, N Milinkovic, Z Lazic, A Ivosevic, D Radojkovic, A Divac Rankov
• Journal: Pulmonology (Pulmonology) 2024 Mar-Apr Vol. 30 Issue 2 Pg. 122-129 ISSN: 2531-0437 [Electronic] Spain
• PMID: 34674978 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

Chemical References

• Methionine Sulfoxide Reductases
• Pancreatic Elastase
• methionine sulfoxide reductase
• SERPINA1 protein, human

Topics

• Adult
• Humans
• Methionine Sulfoxide Reductases (genetics)
• Oxidative Stress
• Pancreatic Elastase (genetics)
• Polymorphism, Genetic
• Pulmonary Disease, Chronic Obstructive (genetics)