Summary. Host genetic factors and environment factors including hepatitis B virus (HBV) genotypes are widely studied for the different outcomes of HBV infection. Recent studies suggest that tumour necrosis factor‐alpha (TNF‐alpha) plays a pivotal role in the viral clearance and host immune response to HBV, and the capacity for TNF‐alpha production in individuals is influenced by a major genetic component. In this study, we aimed to explore whether the single‐nucleotide polymorphisms (SNPs) of TNF‐alpha promoter are associated with the outcomes of HBV infection in the Chinese Han population. One hundred and forty‐three spontaneously recovered HBV subjects and 196 chronic hepatitis B patients were recruited in this case–control study in the Beijing area of China. Polymerase chain reaction–restriction fragment‐length polymorphism (PCR‐RFLP) and sequence‐specific primer‐PCR (SSP‐PCR) were used to detect the SNPs of five sites in the TNF‐alpha promoter (−238G/A, −308G/A, −857C/T, −863C/A, −1031T/C). The frequency distributions of genotypes and haplotypes in two groups were analysed by EPI and EH programs. The presence of the −238GG genotype was significantly correlated with persistence of HBV infection (OR = 4.08, P = 0.02), and −857TT genotype appeared in relation to the spontaneous clearance of HBV (OR = 0.47, P = 0.03). Frequency of haplotype GGCCT (−238/−308/−857/−863/−1031) in the chronic HB group was significantly lower than that in spontaneously recovered group (P = 0.03), and frequencies of haplotypes GGCAT and GGTAT in the chronic HB group were significantly higher than those in the spontaneously recovered group (P = 0.0001, P = 0.0004). In conclusion, TNF‐alpha promoter polymorphisms are independently associated with different outcomes of HBV infection.
