Genetic polymorphism of Epoxide hydrolase and glutathione S-transferase in COPD patients

Abstract

Introduction: Genetic susceptibility to the development of chronic obstructive pulmonary disease (COPD) might depend on variation in the activities of enzymes that detoxify cigarette smoke products, such as microsomal epoxide hydrolase (mEPHX) and glutathione S-transferase (GST). Purpose: To investigate effect of mEPHX, GSTM1, GSTT1, and GSTP1 gene polymorphisms on COPD susceptibility and it`s interaction with smoking dose. Materials and methods: Eighty patients with COPD and eighty healthy subjects who were smokers or ex-smokers enrolled in the case-control study. Genotyping was performed in all participants using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) technique. Results: GSTM1-null genotypes were significantly higher in patients with COPD than in control subjects (OR=2.03, 95% CI, 1.08-3.82, p=0.027). Participants who had a smoking index >800 had five times (OR=5.54, 95% CI, 2.23-13.76, p=0.0005) higher risk for COPD compared to people who had a lower smoking index (<400). No significant associations were observed for GSTP1 and GSTT1 gene polymorphisms with COPD. On additive interaction analysis, a significant positive interactive effect of GSTM1-null and rs1051740 polymorphism with smoking was observed in Mongolian population (RERI=1.787, AP=0.218, S=1.33). Conclusion: This study demonstrated that GSTM1 deletion and rs1051740 polymorphism in mEPHX gene significantly interacted with smoking, and that both in association lead to an increased risk for COPD in the Mongolian population.