Association between chronic hepatitis B virus infection and interleukin-10, tumor necrosis factor-alpha gene promoter polymorphisms

Abstract

Background: The reasons for the viral persistence of hepatitis B virus infection (HBV) are unknown, but are probably related to host immune factors. Cytokines play a significant role in immune defense. The present study was undertaken to investigate the association between HBV infection and polymorphisms of tumor necrosis factor (TNF)-alpha and interleukin(IL)-10 gene promoter.

Methods: A total of 412 Korean patients with HBV infection (72 inactive carriers, 261 with chronic hepatitis, 79 with liver cirrhosis) and 204 healthy individuals who recovered from HBV infection, were studied. The polymorphisms in IL-10 gene promoter (-1082, -819, -592), and TNF-alpha gene promoter (-308, -238) were assessed by single base primer extension assay.

Results: The frequency of C/C genotype at position -592 of IL-10 gene promoter was higher in the HBV clearance group than that in the persistence group in univariate analysis (12.7% vs 7.5%, P = 0.036). The IL-10 gene promoter -592 C/C genotype was related to clearance of HBV infection in logistic regression analysis after adjusting for age and sex (P = 0.003). 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, but in multivariate analysis after adjusting for age and sex, -308G/-238G homozygotes were associated with HBV persistence (P = 0.005). Genotype distributions of both gene promoters in inactive carriers were similar to those in patients with chronic progressive liver disease.

Conclusions: The carriers of the -592A allele in the IL-10 promoter and -308G/-238G haplotype homozygotes in the TNF-alpha promoter region have higher risk of persistent HBV infection.