The Association Between Polymorphic Genotypes of Glutathione S-Transferases and COPD in the Turkish Population |
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Authors: | Mukadder Çal?koglu Lülüfer Tamer Nurcan Ates Aras Sevim Karaka? Bahad?r Ercan |
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Institution: | (1) Department of Chest Disease, Mersin University Faculty of Medicine, 33079 Mersin, Turkey;(2) Department of Biochemistry, Mersin University Faculty of Medicine, Mersin, Turkey;(3) Department of Medical Biology, Mersin University Faculty of Medicine, Mersin, Turkey |
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Abstract: | Although smoking is regarded as the most important causal factor in chronic obstructive pulmonary disease (COPD), only 10–20%
of smokers develop symptomatic COPD, which indicates the presence of genetic predisposing factors in its pathogenesis. This
study investigates the association between gene polymorphysims of glutathione S-transferases (GSTs) and COPD. Blood samples were taken from 149 patients and 150 healthy controls. Polymorphisms of GSTT1,
GSTM1, and GSTP1 were genotyped using Real-Time PCR. Multivariate logistic regression was used to calculate odds ratios (ORs)
and 95% confidence intervals between specific genotypes and COPD. There was no difference in the frequencies of the genotypes
of GSTM1 and GSTT1 between the groups, but the GSTP1 Ile/Ile genotype was significantly higher in the patients than in the
controls (61.1% vs. 38%). GSTP1 Ile/Val and Val/Val genotypes were associated with a decreased risk of COPD when compared
to the Ile/Ile genotype (2.12-fold and 4-fold, respectively). Thus we suggest that the Val allele of GSTP1 may have a protective
effect for development of COPD. Furthermore, when we evaluated the association between GSTP1 genes and smoking status, smokers
with the GSTP1 Ile allele had an increased risk for the development of COPD. Among the combinations of the genotypes, the
combination of GSTM1, GSTT1 null, and GSTP1 Val/Val was associated with the maximal increased risk (12-fold) of COPD. Thus
to explain the ethiopathogenesis of COPD, investigation of a single gene family is inadequate. Based on our results and the
previous data, further studies should be focused on the GSTP1 gene and the interactions with other genes such as polymorphisms
of N-acetyltransferases, GSTM1 and GSTT1, microsomal epoxide hydrolase, and allelic variants of cytochrome P450. |
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Keywords: | glutathione S-transferase chronic obstructive pulmonary disease smoking |
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