A study of TNF-alpha-238 and -308 polymorphisms with different outcomes of persistent hepatitis B virus infection in China

Abstract

Background: Two common functional polymorphisms in the promoter region of TNF-α located at nucleotides -238 (rs361525) and -308 (rs1800629) have been reported to regulate the expression of tumour necrosis factor alpha (TNF-α) and to be associated with hepatitis B virus (HBV) infection related diseases. However, their frequencies and associations with outcomes of HBV infection are not clear.

Methods: We performed a genetic analysis of 956 Chinese Han subjects, who were divided into a HBV clearance group, an asymptomatic persistent infection group, a chronic hepatitis B group, two stages of liver cirrhosis (LC) groups, and three stages of hepatocellular carcinoma (HCC) groups to examine the relationship among HBV infection related diseases and these two single nucleotide polymorphisms (SNPs).

Results: The phenotype of polymorphism -238 in all study samples displayed no significant differences among the eight subgroups. The distribution of -308 phenotypes among the eight groups differed significantly. For females, compared with persistent infection, LC patients had a significantly higher A allele frequency, and the association with cirrhosis progression was significant. For males, there were statistically significant differences in allele distributions between the persistent infection group and the HCC group. The AG haplotype (-A308, -G238) was associated significantly with HCC development.

Conclusions: The results of the present study indicate an association between rs1800629 and HBV related disease progression in the Chinese Han population. The association was different between genders, with the rs1800629 A allele being a risk factor for female carriers to develop LC, and the allele being a risk factor for male carriers to develop HCC, especially in subjects with an alcohol abuse or cigarette smoking history.