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Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients
dc.creator | Milovanović, Vera | |
dc.creator | Topić, Aleksandra | |
dc.creator | Milinković, Neda | |
dc.creator | Lazić, Zorica | |
dc.creator | Ivošević, Anita | |
dc.creator | Radojković, Dragica | |
dc.creator | Divac Rankov, Aleksandra | |
dc.date.accessioned | 2021-12-09T10:33:08Z | |
dc.date.available | 2021-12-09T10:33:08Z | |
dc.date.issued | 2024 | |
dc.identifier.issn | 2173-5115 | |
dc.identifier.uri | https://farfar.pharmacy.bg.ac.rs/handle/123456789/4003 | |
dc.description.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. | sr |
dc.language.iso | en | sr |
dc.publisher | Elsevier | sr |
dc.relation | info:eu-repo/grantAgreement/MESTD/inst-2020/200161/RS// | sr |
dc.relation | info:eu-repo/grantAgreement/MESTD/inst-2020/200042/RS// | sr |
dc.rights | openAccess | sr |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.source | Pulmonology | sr |
dc.subject | MSRA | sr |
dc.subject | Polymorphism | sr |
dc.subject | Chronic obstructive pulmonary disease | sr |
dc.subject | Oxidatively modified alpha-1-antitrypsin | sr |
dc.subject | Specific inhibitor activity to elastase | sr |
dc.title | Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients | sr |
dc.type | article | sr |
dc.rights.license | BY-NC-ND | sr |
dc.citation.volume | 30 | |
dc.citation.issue | 2 | |
dc.citation.spage | 122 | |
dc.citation.epage | 129 | |
dc.identifier.doi | 10.1016/j.pulmoe.2021.09.003 | |
dc.identifier.scopus | 2-s2.0-85120634126 | |
dc.identifier.fulltext | http://farfar.pharmacy.bg.ac.rs/bitstream/id/9296/bitstream_9296.pdf | |
dc.type.version | publishedVersion | sr |