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Persistent hepatitis B virus infection is a major risk factor for hepatocellular carcinoma, the most frequent cancer in some developing countries. Up to 95% of those infected at birth and 15% of those infected after the neonatal period fail to clear hepatitis B virus, together resulting in approximately 350 million persistent carriers worldwide. Via a whole genome scan in Gambian families, we have identified a major susceptibility locus as a cluster of class II cytokine receptor genes on chromosome 21q22. Coding changes in two of these genes, the type I IFN receptor gene, IFN-AR2, and the IL-10RB gene that encodes a receptor chain for IL-10-related cytokines including the IFN-lambdas, are associated with viral clearance (haplotype P value = 0.0003), and in vitro assays support functional roles for these variants in receptor signaling.

Original publication

DOI

10.1073/pnas.0602800103

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

13/06/2006

Volume

103

Pages

9148 - 9153

Keywords

Carcinoma, Hepatocellular, Carrier State, Cell Line, Gambia, Genetic Markers, Genetic Predisposition to Disease, Genotype, Hepatitis B, Chronic, Humans, Linkage Disequilibrium, Liver Neoplasms, Membrane Proteins, Multigene Family, Polymorphism, Genetic, Receptor, Interferon alpha-beta, Receptors, Cytokine, Receptors, Interferon, Receptors, Interleukin, Receptors, Interleukin-10, Sequence Analysis, DNA, Tumor Necrosis Factor-alpha