Polymorphisms of glutathione S-transferase M1, T1, and P1 in patients with HBV-related liver cirrhosis, chronic hepatitis, and normal carriers

Abstract

Objectives: Persistent hepatitis B virus (HBV) infection often leads to the development of chronic hepatitis and cirrhosis. The role of host genetic factors in chronic HBV infection is not fully understood. We studied the influence of glutathione S-transferase (GST) M1, T1, and P1 polymorphisms in patients with different stages of HBV infections. Methods: The sample population included 41 HBV normal carriers, 37 patients with chronic hepatitis, and 38 patients with cirrhosis (infected with HBV) compared to a control group ( n = 59). PCR-based procedures were performed in the studied populations to confirm the genotypes of GSTT1, M1, and P1. Odds ratio analysis tests were used for statistical evaluation. Results: We found that the frequency of GSTP1-Val (105)/Val (105) genotype was significantly higher in patients with liver cirrhosis (27%) than HBV normal carriers (2.4%; OR 14.8, 95% CI 1.8–122.5) and the frequency GSTP1-Val (105)/Ile (105) genotype was significantly higher in patients with liver cirrhosis (59.5%) than HBV normal carriers (19.5%; OR 6.1, 95% CI 2.1–16.7). The genotype GSTP1-Val (105)/Val (105) was more frequent in patients with chronic hepatitis (19.4%) than HBV normal carriers (2.4%; OR 9.65, 95% CI 1.1–82.8). Patients with cirrhosis also had a higher frequency of the GSTM1 null genotype (71.1%) than HBV normal carriers (27.5%; OR 6.5, 95% CI 2.4–17.4) and the GSTM1 null genotype was more frequent in patients with chronic hepatitis (64.9%) than HBV normal carriers (27.5%OR 4.9, 95% CI 1.8–12.8). The frequency of GSTT1 genotype was similar in all groups. Conclusion: These results suggest that in HBV infection, inheritance of the null GSTM1 and GSTP1-Val (105) polymorphisms involves a host genetic factor that is relevant to disease progression.