Association between chronic hepatitis B virus infection and tumor necrosis factor-alpha gene promoter polymorphisms / 대한내과학회지

ABSTRACT

BACKGROUND: The reasons for the viral persistence and disease progression of hepatitis B virus (HBV) infection are unknown, but are probably related to host immune factors. Cytokines such as tumor necrosis factor-alpha (TNF-alpha) play significant roles in inflammatory and immune defense. This study was undertaken to investigate the association between HBV infection and polymorphisms of TNF-alpha gene promoter polymorphism. METHODS: We studied 412 Korean patients with chronic HBV infection (72 inactive carriers, 261 chronic hepatitis, 79 liver cirrhosis) and 204 healthy individuals who recovered from HBV infection. We assessed two biallelic polymorphisms in TNF-alpha gene promoter (at position -308, -238) by single base primer extension assay (SNP ITTM). RESULTS: Genotype frequencies of TNF-alpha gene promoter at position -308 and -238 were not different between the clearance and the persistence group in univariate analysis. In multivariate analysis after adjusting age and sex, TNF 308 G/G genotype was associated with HBV persistence (ORs;1.71, p=0.039). Moreover, concerning the haplotype analysis, -308G/ -238G homozygotes showed much higher correlation with HBV persistence (ORs;1.88, p=0.005). Genotype distributions of both gene promoters in inactive carriers were similar to those in patients with chronic progressive liver disease (chronic hepatitis and liver cirrhosis). CONCLUSION: The carriers of -308 G/G genotype and -308G / -238G haplotype homozygotes in the TNF-alpha promoter region have higher risk of persistent HBV infection.