Glutathione S-Transferase M1 and T1 Gene Polymorphisms and the Outcome of Chronic Hepatitis C Virus Infection in Egyptian Patients

Abstract

We analysed the distribution of GSTM1 and GSTT1 gene polymorphisms in Egyptian patients with chronic hepatitis C, and investigated their relationship to the clinical outcome of chronic hepatitis C virus (HCV) infection. This study included 169 patients with chronic HCV infection and 145 healthy and matched controls.GSTM1 and GSTT1 polymorphisms were genotyped by multiplex polymerase chain reaction. Individual GSTM1 null and GSTT1 null genotypes were more frequent in patients versus control subjects [OR, 4 (95% CI, 2.5-6.4); P ˂ 0.001] and [OR, 1.7 (95% CI, 1.1-2.6); P = 0.025], respectively. The patient group showed a higher frequency of the combined GSTM1/GSTT1 double-null genotype than the control group [OR, 1.8 (95% CI, 1.1-2.9); P = 0.016]. The distribution frequencies of the combined GSTM1/GSTT1 double-null genotype were significantly different [OR, 0.5 (95% CI, 0.25-0.99); P = 0.049] between F0-F3 and F4. There were no significant differences between the two groups with regard to other genotypes. The combined GSTM1/GSTT1 double-null genotype was significantly increased in Child-Pugh C patients in comparison to Child-Pugh A+B (P = 0.02). There was no significant difference between different classes with regard to other genotypes. In conclusion, we identified an association between the combined GSTM1/GSTT1 double-null genotype and advanced liver fibrosis and outcome of chronic HCV infection in Egyptian patients.

Association of Polymorphisms in the Glutathione S-Transferase Theta-1 Gene with Cirrhosis and Hepatocellular Carcinoma in Brazilian Patients with Chronic Hepatitis C

“…Interestingly, GSTT1 has glutathione peroxidase activity and may be directly involved in detoxification of reactive species produced as a consequence of ongoing HCV infection of the liver [ 24 , 30 ]. Notably, two previous studies evaluating the association of GSTM1 and GSTT1 polymorphisms with progression of liver disease in Egyptian [ 23 ] and Taiwanese [ 25 ] patients with chronic HCV showed considerably increased risk of advanced fibrosis in individuals with combined GSTM1 / GSTT1 double-null genotype. Here, the GSTM1 / GSTT1 double-null genotype was more frequently detected in patients with HCC than those with chronic hepatitis (10% vs. 2.1%, respectively) but this difference was not statistically significant.…”

“…Limited published data are available on the influence of GST polymorphisms in the late stages of HCV infection, specifically, development of cirrhosis and HCC [ 23 , 24 , 25 ], and no studies have been conducted on the Brazilian population to date. In this study, we determined the distribution of GSTM1 and GSTT1 polymorphisms in patients with chronic HCV grouped according to stage of liver disease (chronic hepatitis, cirrhosis, and HCC), with a view to investigating their potential involvement in risk of disease progression in Brazilian patients with chronic hepatitis C infection.…”

Polymorphism of Glutathione S-transferase Genes and the Risk of Toxic Liver Damage in Petrochemical Workers

“…The contribution of these genetic polymorphisms to human susceptibility to hepatitis of various etiologies and liver cirrhosis has already been shown. 5,6 We conducted this study to elucidate the association between polymorphism in glutathione S-transferase genes (GSTM1, GSTT1 and GSTP1) and the risk of toxic liver damage in a group of petrochemical workers.…”