Genetic susceptibility of glutathione S-transferase genes (GSTM1/T1 and P1) to coronary artery disease in Asian Indians

Abstract

Genetic polymorphisms in glutathione S-transferase (GST) genes may modulate the risk of cardiovascular diseases. The objective of present study was to investigate the potential association between the polymorphisms of GSTM1/T1 and P1 genes and their influence on diverse clinical parameters and oxidative stress biomarkers in coronary artery disease (CAD) patients in Asian Indians. The present study includes 562 angiographically confirmed CAD patients and 564 healthy control subjects from the north Indian population. Anthropometric and clinical measurements were performed for all the participants. The oxidative stress biomarkers including malondialdehyde and total antioxidant capacity were also measured. The genotyping of the GSTM1/T1 and P1 genes was performed using the multiplex-PCR and PCR-RFLP methods. The CAD patients exhibit significantly high values of waist circumference, waist-to-hip ratio, body fat (%), glucose, triglycerides, and very low-density lipoprotein, and reduced high-density lipoprotein levels compared to control subjects (P < 0.001). Malondialdehyde levels were significantly enhanced, and the total antioxidant capacity was reduced in CAD patients compared to controls (P < 0.001). However, no significant difference in body mass index and total cholesterol levels were observed in CAD patients and control subjects. The frequencies of the GSTM1 and GSTM1/T1 null genotypes in the CAD patients were significantly higher than the control subjects. In contrast, the GSTT1(-) genotype frequencies were significantly lower in CAD patients than the controls. Logistic regression analysis of the data revealed the null genotype of GSTM1 and the GG genotype of the GSTP1 (313A/G) gene were associated with an approximately twofold enhanced risk of developing CAD, whereas GSTT1(-) plays a defensive role against CAD development in north Indians. Upon stratification of data according to the genotypes of the GSTM1/T1 and P1 genes, we did not find significant a difference among the various metabolic traits in CAD patients and controls. Our results suggest that oxidative damage induced by lipid peroxidation with reduced antioxidant capacity and genetic variants in GST genes (GSTM1/T1 and P1) may modify the risk of CAD development in Asian Indian population.

Keywords: GSTs; Indian population; coronary artery disease; gene polymorphism; oxidative stress.