Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients
Autori
Milovanović, VeraTopić, Aleksandra
Milinković, Neda
Lazić, Zorica
Ivošević, Anita
Radojković, Dragica
Divac Rankov, Aleksandra
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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.
Ključne reči:
MSRA / Polymorphism / Chronic obstructive pulmonary disease / Oxidatively modified alpha-1-antitrypsin / Specific inhibitor activity to elastaseIzvor:
Pulmonology, 2021Izdavač:
- Elsevier
Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200161 (Univerzitet u Beogradu, Farmaceutski fakultet) (RS-200161)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200042 (Univerzitet u Beogradu, Institut za molekularnu genetiku i genetičko inženjerstvo) (RS-200042)
Institucija/grupa
PharmacyTY - JOUR AU - Milovanović, Vera AU - Topić, Aleksandra AU - Milinković, Neda AU - Lazić, Zorica AU - Ivošević, Anita AU - Radojković, Dragica AU - Divac Rankov, Aleksandra PY - 2021 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4003 AB - 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. PB - Elsevier T2 - Pulmonology T1 - Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients DO - 10.1016/j.pulmoe.2021.09.003 ER -
@article{ author = "Milovanović, Vera and Topić, Aleksandra and Milinković, Neda and Lazić, Zorica and Ivošević, Anita and Radojković, Dragica and Divac Rankov, Aleksandra", year = "2021", 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.", publisher = "Elsevier", journal = "Pulmonology", title = "Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients", doi = "10.1016/j.pulmoe.2021.09.003" }
Milovanović, V., Topić, A., Milinković, N., Lazić, Z., Ivošević, A., Radojković, D.,& Divac Rankov, A.. (2021). Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients. in Pulmonology Elsevier.. https://doi.org/10.1016/j.pulmoe.2021.09.003
Milovanović V, Topić A, Milinković N, Lazić Z, Ivošević A, Radojković D, Divac Rankov A. Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients. in Pulmonology. 2021;. doi:10.1016/j.pulmoe.2021.09.003 .
Milovanović, Vera, Topić, Aleksandra, Milinković, Neda, Lazić, Zorica, Ivošević, Anita, Radojković, Dragica, Divac Rankov, Aleksandra, "Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients" in Pulmonology (2021), https://doi.org/10.1016/j.pulmoe.2021.09.003 . .