Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients
V. Milovanovic , A. Topic , N. Milinkovic , Z. Lazic , A. Ivosevic , D. Radojkovic , A. Divac Rankov
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引用次数: 0
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.
PulmonologyMedicine-Pulmonary and Respiratory Medicine
CiteScore
14.30
自引率
5.10%
发文量
159
审稿时长
19 days
期刊介绍:
Pulmonology (previously Revista Portuguesa de Pneumologia) is the official journal of the Portuguese Society of Pulmonology (Sociedade Portuguesa de Pneumologia/SPP). The journal publishes 6 issues per year and focuses on respiratory system diseases in adults and clinical research. It accepts various types of articles including peer-reviewed original articles, review articles, editorials, and opinion articles. The journal is published in English and is freely accessible through its website, as well as Medline and other databases. It is indexed in Science Citation Index Expanded, Journal of Citation Reports, Index Medicus/MEDLINE, Scopus, and EMBASE/Excerpta Medica.