Genetic polymorphisms of CYP2E1 and DNA repair genes HOGG1 and XRCC1: association with hepatitis B related advanced liver disease and cancer

Abstract

A population based case-control study was designed to explore the genetic risk factors for hepatitis B virus (HBV) related liver disease susceptibility. A total of 424 subjects comprising 210 controls, 50 acute HBV (AVH), 84 chronic HBV (CHBV), 25 HBV related cirrhosis and 55 HBV related hepatocellular carcinoma (HCC) cases were included in the study. PCR-RFLP was used for the genotyping of Cyp2E1*5B, hOGG1 codon 326 and XRCC1 codon 399. Compared to controls, Cyp2E1 rsaI variant c2 genotype increased the risk of HBV related liver disease severity by 2.68 fold, the highest for HCC cases (3.981 folds, p=0.106); and was associated with higher histology activity index (HAI) (p<0.001) in CHBV patients. Cyp2E1 and hOGG1 variants were independently associated with a significantly higher fibrosis score in CHBV group. Analysis of gene-gene interaction studies showed an increased risk of HCC, cirrhosis and CHBV in a Cyp2E1 variant+XRCC1 variant combination (p<0.001); and hOGG1 variants+XRCC1 variants. A mutually independent heterozygous hOGG1 and XRCC1 combination resulted in a decreased risk of HBV related liver disease. On the other hand, a wild-type hOGG1 and XRCC1 combination was associated with a significantly higher risk of AVH (p=0.010) but a lower risk of CHBV (p=0.032) and HCC (p=0.006). The gene-gene interactions were also associated with a significant increase in HAI and fibrosis score in CHBV patients. Cyp2E1, hOGG1 and XRCC1 genotypes significantly alter the risk of HBV related liver disease susceptibility and severity, independently or through gene-gene interaction.