Abstract: ObjectiveTo determine whenther-238 G/A,-857 T/C and-863C/A polymorphisms of tumor necrosis factor-alphya(TNF-α)gene promoter were associated with outcomes of hepatitis B virus(HBV)infection.MethodA total of 244 HBV self-limited infected subjects,212 asymptomatic HBsAg carriers(HBsAg carriers)and 391 chronic hepatitis B(HB)patients were recruited to conduct a case-control study.TNF-α-238 G/A,-857C/T and-863C/A gene promoter polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).ResultsThe frequency of-238 allele A in self-limited individuals was 2.6%,significantly lower than 5.0% in chronic HB patients and 5.3% in HBsAg carriers(P=0.04 and P=0.047),respectively.The frequency of TNF-α-857 allele C in chronic HB patients was 87.5%,significantly higher than 80.5% in HBsAg carriers and 82.8% in self-limited individuals(P=0.0008 and P=0.03),respectively.The frequency of TNF-α-863 allele A in chronic HB group was 77.5%,significantly higher than 71.5% in HBsAg carriers(P=0.02).Multiple logistic regression analyses indicated an increased risk of chronic HB associated with TNF-α-238 GA and-857CC after gender and age adjusting(OR=1.53,P=0.044;OR=2.11,P=0.045),and HBsAg carriers wit -857CC significantly increasing risk of chronic HB associated with TNF-α-238 GA and -857CC after gender and age adjusting(OR=1.53,P=0.044;OR=2.11,P=0.045),an HBsAg carriers with-857CC significantly increasing risk of chronic HB(OR=1.92,P=0.004),and-238 GA associated with and increasing risk of HBsAg carriers(OR=2.34,P=0.020).ConclusionTNF-αpromoter polymorphism is probably an important risk factor of the influence of outcome of HBV infection.