Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients
Copyright © 2021 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Pulmonology - 30(2024), 2 vom: 28. März, Seite 122-129 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Milovanovic, V [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.03.2024 Date Revised 05.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.pulmoe.2021.09.003 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 245 | 1 | 0 | |a Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients |
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| 500 | |a Date Revised 05.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chronic obstructive pulmonary disease | |
| 650 | 4 | |a MSRA | |
| 650 | 4 | |a Oxidatively modified alpha-1-antitrypsin | |
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| 700 | 1 | |a Ivosevic, A |e verfasserin |4 aut | |
| 700 | 1 | |a Radojkovic, D |e verfasserin |4 aut | |
| 700 | 1 | |a Rankov, A Divac |e verfasserin |4 aut | |
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