Association of TNF-α promoter polymorphisms with the outcome of persistent HBV infection in a northeast Chinese Han population

Tumor necrosis factor-α （TNF-α ）plays an important role in the pathogenesis and clinical outcome of chronic hepatitis B virus （HBV） infection. The objective of this study was to evaluate the relationship between functional polymorphisms of TNF-α and different outcomes of persistent HBV infection in a northeast Chinese Han population. Here 189 HBV spontaneously recovered subjects （SR）, 571 HBV-infected patients including 180 chronic hepatitis B （CHB）, 196 liver cirrhosis （LC）, and 195 hepatocellular carcinoma （HCC） individuals were enrolled in this study. All the samples were genotyped for TNF-α -857C/T and -863C/A using the polymerase chain reaction-restriction fragment length polymorphism method. The frequency of -857CC genotype was significantly higher in CHB and LC individuals compared with that of SR subjects （P = 0.03, OR = 1.57, 95% CI 1.04-2.39 and P = 0.03, OR = 1.57, 95% CI 1.04-2.35, respectively）. A significant dif- ference in the distribution of the allele -857C was observed for both CHB vs. SR （P = 0.01, OR = 1.52, 95% CI 1.08-2.13） and LC vs. SR （P = 0.02, OR = 1.47, 95% CI 1.06-2.04） cohorts. In addition, the frequency of -863AA genotype was significantly higher in CHB and LC patients than that of SR subjects （P = 0.01, OR = 3.90, 95% CI 1.35-11.23 and P = 0.01, OR = 3.83, 95% CI 1.34-10.96, respectively）, and allele -863A frequency was significantly more common in CHB, LC, and HCC cohorts than that of SR controls （P = 0.004, OR = 1.72, 95% CI 1.19-2.50; P = 0.001, OR = 1.81, 950/0 CI 1.26- 2.61 and P = 0.001, OR = 1.90, 95% CI 1.33-2.73, re- spectively）. Our data also revealed that haplotype CA was strongly associated with persistent HBV infection. These results suggest an association between the TNF-α promoter variants and different outcomes of persistent HBV infection in the studied population.