Interleukin 12B gene polymorphism and apparent resistance to hepatitis C virus infection.

Cellular immunity with interferon gamma production could have a role in protection from hepatitis C virus (HCV). Interleukin (IL)-12 is a key cytokine in promoting such anti-viral T helper 1 (Th1) responses. We hypothesized that a genetic background able to promote cellular responses may be associated with apparent protection from infection and have investigated the distribution of the functional 1188A/C polymorphism of IL-12B in HCV exposed but uninfected cases. The frequency of the high IL-12-producing C allele was determined by restriction enzyme genotyping in 76 exposed-uninfected individuals and 105 healthy controls. Overall, the C allele was found in 27.6% of exposed-uninfected cases compared with 16.7% of healthy controls [chi(2) = 6.3, P = 0.02, odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.1-3.2]. CC genotype was found in 10.5% of exposed-uninfected cases compared with 0.9% controls (chi(2) = 9.3, P = 0.01, OR = 12, 95% CI = 1.5-100). Individuals at high risk of HCV infection yet who remain uninfected may be resistant in some way to infection. In our cohort of exposed-uninfected cases a genetic background of enhanced IL-12 production was associated with apparent resistance to HCV infection. This lends support to a central role for cellular immune responses in protecting from infection.