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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 | Milovanovic, V. | |
dc.creator | Topic, A. | |
dc.creator | Milinkovic, N. | |
dc.creator | Lazic, Z. | |
dc.creator | Ivosevic, A. | |
dc.creator | Radojkovic, D. | |
dc.creator | Divac Rankov, Aleksandra | |
dc.date.accessioned | 2022-12-28T10:56:31Z | |
dc.date.available | 2022-12-28T10:56:31Z | |
dc.date.issued | 2024 | |
dc.identifier.issn | 2531-0437 | |
dc.identifier.uri | https://imagine.imgge.bg.ac.rs/handle/123456789/1647 | |
dc.description.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. | |
dc.language | en | |
dc.publisher | Elsevier | |
dc.relation | info:eu-repo/grantAgreement/MESTD/inst-2020/200161/RS// | |
dc.relation | info:eu-repo/grantAgreement/MESTD/inst-2020/200042/RS// | |
dc.rights | openAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.source | Pulmonology | |
dc.source | Pulmonology | |
dc.subject | Chronic obstructive pulmonary disease | |
dc.subject | MSRA | |
dc.subject | Oxidatively modified alpha-1-antitrypsin | |
dc.subject | Polymorphism | |
dc.subject | Specific inhibitor activity to elastase | |
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 | |
dc.type | article | en |
dc.rights.license | BY-NC-ND | |
dc.citation.epage | 129 | |
dc.citation.issue | 2 | |
dc.citation.rank | M21 | |
dc.citation.spage | 122 | |
dc.citation.volume | 30 | |
dc.identifier.doi | 10.1016/j.pulmoe.2021.09.003 | |
dc.identifier.fulltext | https://imagine.imgge.bg.ac.rs/bitstream/id/27190/Association.pdf | |
dc.identifier.scopus | 2-s2.0-85120634126 | |
dc.type.version | publishedVersion |