Polymorphism in glutathione-S-transferases: A risk factor in alcoholic liver cirrhosis

Abstract

In a case-control study, association of polymorphism in glutathione-S-transferases ( GSTM1, GSTT1, GSTP1), involved in detoxification of reactive oxygen species (ROS), was studied with alcoholic liver cirrhosis. The study included 175 alcoholic cirrhotic patients (ACPs), 140 non-alcoholic cirrhotic patients (NACPs), visiting Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI), Lucknow, India, 255 non-alcoholic controls and 140 alcoholic controls. The data showed an increase in risk to alcoholic cirrhosis in ACPs with GSTM1 ( null) genotype when compared with non-alcoholic controls (OR: 1.7; 95% CI: 1.15–2.56) or alcoholic controls (OR: 1.7; 95% CI: 1.07–2.73). Significant increase in risk was also observed in ACPs with variant genotype of GSTP1 when compared with non-alcoholic controls (OR: 1.65; 95% CI: 1.12–2.43). A much higher risk to alcoholic liver cirrhosis was observed in patients carrying combination of null genotypes of GSTM1 and GSTT1 (OR: 2.8; 95% CI: 1.3–6.06) or variant genotype of GSTP1 and null genotype of GSTM1 (OR: 2.8; 95% CI: 1.58–4.90) or GSTT1 (OR: 2.16; 95% CI: 1.08–4.28). Likewise, greater risk for alcoholic cirrhosis was observed in patients carrying combination of GSTM1, GSTT1 ( null) and variant genotype of GSTP1 (OR: 5.8; 95% CI: 2.17–15.80). Our data further showed that interaction of GSTs with variant genotype of manganese superoxide dismutase ( MnSOD), which detoxifies free radicals, or cytochrome P450 2E1, which generates free radicals, resulted in several fold increase in risk to alcoholic liver cirrhosis in ACPs when compared with non-alcoholic controls thus demonstrating the role of gene–gene interactions in modulating the risk to alcoholic liver cirrhosis.