Class II cytokine receptor gene cluster is a major locus for hepatitis B persistence.

Angela J Frodsham; Lyna Zhang; Uga Dumpis; Nor Azizah Mohd Taib; Steve Best; Andrew Durham; Branwen JW Hennig; Simon Hellier; Susanne Knapp; Mark Wright; +7 more... Maria Chiaramonte; John I Bell; Mary Graves; Hilton C Whittle; Howard C Thomas; Mark R Thursz; Adrian VS Hill; (2006) Class II cytokine receptor gene cluster is a major locus for hepatitis B persistence. Proceedings of the National Academy of Sciences of the United States of America, 103 (24). pp. 9148-9153. ISSN 0027-8424 DOI: 10.1073/pnas.0602800103

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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.