The Association Between Polymorphic Genotypes of Glutathione S-Transferases and COPD in the Turkish Population

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.

Association of GSTM1 and GSTT1 Polymorphisms with Chronic Obstructive Pulmonary Disease in a Tunisian Population

“…Our findings are in line with numerous studies that report a nonsignificant association between a deletion of the GSTM1 gene and this pathogenesis (Chen et al 1996;Ž idzik et al 2008;Hersh et al 2005;Calikoglu et al 2006;Chan-Yeung et al 2007). The results of Cheng et al (2004), however, document that the GSTM1-null genotype is an independent risk factor for developing COPD.…”

“…The results of Cheng et al (2004), however, document that the GSTM1-null genotype is an independent risk factor for developing COPD. On the other hand, some authors report that a combination of both a homozygous deletion of the GSTM1 gene and mutation of other genes involved in the detoxifying process (such as GSTP1) and microsomal epoxide hydrolase (mEPHX) contributes significantly to the risk of chronic obstructive lung disease (Lu and He 2002;Ž idzik et al 2008;Calikoglu et al 2006). Our analysis of the combined GSTT1 and GSTM1 null alleles showed no significant association between the double deletion and an increased risk of COPD.…”

Chronic Obstructive Pulmonary Disease and Lung Cancer: New Molecular Insights

“…In addition, smokers with the GSTP1 Ile allele have an increased risk for the development of COPD [95]. Furthermore, the combination of GSTM1, GSTT1 null, and GSTP1 Val/Val is associated with the maximal increased risk (12-fold) of COPD [95]. …”

XRCC1 Arg194Trp polymorphism and risk of chronic obstructive pulmonary disease

“…Therefore, some DNA repair genes may be involved in COPD susceptibility. DNA repair capacity is known to be variable in the human population, and because a part of this variation is believed to be genetic, a number of DNA repair genes have been screened recently and discovered to be polymorphic [14][15][16][17][18][19] . XRCC1, a base excision repair protein that plays a central role in the BER pathway, has multiple roles in repairing ROS-mediated, basal DNA damage and single-strand DNA breaks [20][21][22] .…”