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

Abstract

Oxidative stress contributes to hepatitis C virus (HCV)-induced liver damage. Host genetic factors may be involved in progression of HCV infection. The present study was conducted to determine the influence of glutathione S-transferase (GST)-M1 and T1 gene polymorphisms during different stages of HCV infection, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The study population comprised 190 patients (47 with chronic hepatitis, 83 with cirrhosis (without HCC), and 60 with HCC). GSTM1 and GSTT1 gene polymorphisms were analyzed via multiplex polymerase chain reaction. The GSTT1-null genotype was more commonly detected in patients with cirrhosis (n = 17; 20.5%) and HCC (n = 13; 21.7%) than those with chronic hepatitis (n = 3; 6.4%). The differences in GSTT1-null genotype frequencies were significant for cirrhosis vs. chronic hepatitis (odds ratio, OR, 3.778 (95% confidence interval, CI, 1.045-13.659); p = 0.043) and HCC vs. chronic hepatitis (OR, 4.057 (95% CI, 1.083-15.201); p = 0.038) groups. However, the incidence of individual GSTM1-null or combined GSTM1/GSTT1 double-null genotypes did not vary significantly between the groups. Our collective findings support the utility of the GSTT1-null genotype as a useful biomarker for liver disease progression in Brazilian patients with chronic hepatitis C.

Keywords: cirrhosis; glutathione S-transferases; hepatitis C virus; hepatocellular carcinoma; polymorphisms.

Figure 1

Genotyping of GSTM1 and GSTT1 by multiplex PCR. Lane M: 1 Kb Plus DNA Ladder. Lanes 1, 2 and 6: positive GSTM1 and GSTT1 genotypes. Lane 3: null GSTM1 and GSTT1 genotypes (absence of 215 and 480 bp fragments). Lane 4: null GSTT1 genotype (absence of 480 bp fragment). Lane 5: null GSTM1 genotype (absence of 215 bp fragment). The β-globin internal control is detected as 268 bp fragment.