Association of polymorphism of tumor necrosis factor-alpha gene promoter region with outcome of hepatitis B virus infection.

Aim: To determine whether -238G/A and -857C/T polymorphisms of tumor necrosis factor-alpha (TNF-alpha), gene promoter and hepatitis B (HB) viral genotypes were associated with outcomes of HBV infection.

Methods: A total of 244 HBV self-limited infected subjects, 208 asymptomatic carriers, and 443 chronic HB patients were recruited to conduct a case-control study. TNF-alpha-238G/A and -857C/T gene promoter polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and HBV genotypes were examined by nested PCR.

Results: The positive rate of HBV DNA in asymptomatic carrier group and chronic HB group was 46.6% and 49.9%, respectively. HBV genotype proportion among the asymptomatic carriers was 2.1% for genotype A, 25.8% for genotype B, 68.0% for genotype C, and 4.1% for genotype B+C mixed infection, and 0.9% for genotype A, 21.7% for genotype B, 71.5% for genotype C, 5.9% for genotype B+C mixed infection in chronic HB group. There was no significant difference in genotype distribution between the asymptomatic carrier group and chronic HB group (chi2 = 1.66, P = 0.647). The frequency of -238GG genotype in self-limited group was 95.1%, significantly higher than 90.7% in chronic HB group and 89.0% in asymptomatic carrier group (P = 0.041 and P = 0.016, respectively). The frequency of TNF-alpha-857 CC in chronic HB group was 79.7%, significantly higher than 64.4% in asymptomatic carrier group and 70.9% in self-limited group (P<0.001 and P = 0.023, respectively). A multiple logistic regression analysis revealed that TNF-alpha-238GA and -857CC were independently associated with chronic HB after gender and age were adjusted.

Conclusion: TNF-alpha promoter variants are likely to play a substantial role in the outcome of HBV infection.