Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Carcinoma, Hepatocellular / virology
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Carrier State*
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Cell Line
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Gambia
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Genetic Markers
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Genetic Predisposition to Disease
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Genotype
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Hepatitis B, Chronic* / genetics
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Hepatitis B, Chronic* / immunology
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Humans
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Linkage Disequilibrium
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Liver Neoplasms / virology
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Membrane Proteins / genetics*
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Membrane Proteins / metabolism
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Multigene Family*
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Polymorphism, Genetic
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Receptor, Interferon alpha-beta
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Receptors, Cytokine
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Receptors, Interferon / genetics*
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Receptors, Interferon / metabolism
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Receptors, Interleukin / genetics*
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Receptors, Interleukin / metabolism
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Receptors, Interleukin-10
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Sequence Analysis, DNA
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Genetic Markers
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Membrane Proteins
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Receptors, Cytokine
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Receptors, Interferon
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Receptors, Interleukin
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Receptors, Interleukin-10
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Tumor Necrosis Factor-alpha
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Receptor, Interferon alpha-beta