title: Interleukin 12B gene polymorphism and apparent resistance to hepatitis C virus infection.
abstract: 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.
authors.affiliation: Hepatology and Molecular Medicine Research Groups, Peninsula Medical School, Plymouth University, Plymouth, UK.
authors.forename: D
authors.initials: D
authors.lastname: Hegazy
authors.forename: P
authors.initials: P
authors.lastname: Thurairajah
authors.forename: M
authors.initials: M
authors.lastname: Metzner
authors.forename: A
authors.initials: A
authors.lastname: Houldsworth
authors.forename: S
authors.initials: S
authors.lastname: Shaw
authors.forename: E
authors.initials: E
authors.lastname: Kaminski
authors.forename: A G
authors.initials: AG
authors.lastname: Demaine
authors.forename: M E
authors.initials: ME
authors.lastname: Cramp
mesh_terms: D000328:Adult; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006526:Hepatitis C / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000276:immunology / Q000635:transmission; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D053762:Interleukin-12 Subunit p40 / Q000235:genetics*; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D015819:Substance Abuse, Intravenous / Q000150:complications
chemical_list: C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40