Contribution of Glutathione-S-Transferases Polymorphism and Risk of Coronary Artery Diseases: A Meta-Analysis

Abstract

Background: Oxidative stress is one of the risk components in the development of coronary artery diseases (CAD). Genetic polymorphism in major antioxidant genes like Glutathione- S-Transferases (GST) has been associated with increased CAD susceptibility and severity.

Objective: To get a precise evaluation and to update the association, a meta-analysis on GST (GSTM1, GSTT1, and GSTP1) polymorphism with CAD was performed. Moreover, the combined effect of GSTM1/GSTT1 null genotypes on CAD risk has not yet been studied, but it has the highest risk of developing diseases.

Materials and methods: PubMed, Embase, and Web of Science were systematically searched for eligible studies. Case-control studies in the English language and with genotypic frequency were selected in order to provide data and calculate the odds ratio (OR). OR with 95% CI was calculated, and a random effect model was used. NOS scale was used to assess the quality of the included studies.

Results: Meta-analysis indicated that the GSTM1 null genotype and GSTP1 (Ile105Val) polymorphism is significantly associated with CAD risk with a pooled OR-1.38, p=0.01 for GSTM1 and OR-1.19, p=0.04 for GSTP1. The dual null genotype of GSTM1-GSTT1 has the highest risk for CAD development (OR-1.59, p=0.003), and there is no significant association between GSTT1 null genotype with CAD. In the subgroup analysis, GSTM1 showed an increased risk for Asians (OR- 1.68, p=<0.01) and smokers (OR-1.98, p=<0.01). Publication bias was not observed.

Conclusion: The findings suggest that the GSTM1 and GSTP1 polymorphism can be a predictive factor for CAD risk, and a larger sample size is required further to confirm the association.

Keywords: CAD; GST; ethnicity; gene polymorphism; glutathione-s-transferases; meta-analysis; smoking.