An analysis of tumor necrosis factor alpha gene polymorphisms and haplotypes with natural clearance of hepatitis C virus infection.

The cytokine tumor necrosis factor alpha (TNF-alpha) is important in generating an immune response against a hepatitis C virus (HCV) infection. The functions of TNF-alpha may be altered by single-nucleotide polymorphisms (SNPs) in its gene, TNF. We hypothesized that SNPs in TNF may be important in determining the outcome of an HCV infection. To test this hypothesis, we typed nine TNF SNPs in a cohort of individuals with well-defined HCV outcomes. Three of these SNPs were typed in a second cohort. Data were analyzed using logistic regression stratifying by ethnicity, since rates of HCV clearance differ in black subjects versus white subjects. The SNP -863A was associated with viral clearance in black subjects (odds ratios (OR) 0.52, 95% confidence interval (CI) 0.29-0.93). Furthermore, the common wild-type haplotype -863C/-308G was associated with viral persistence in black subjects (OR 1.91, 95% CI 1.24-2.95). These findings were independent of linkage with human leukocyte antigen (HLA) alleles. Further study of this polymorphism and haplotype is needed to understand these associations and the role of TNF-alpha in determining outcomes of HCV infection.