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

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.

SUBMITTER: Frodsham AJ 

PROVIDER: S-EPMC1482581 | biostudies-literature | 2006 Jun

REPOSITORIES: biostudies-literature

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

Frodsham Angela J AJ   Zhang Lyna L   Dumpis Uga U   Taib Nor Azizah Mohd NA   Best Steve S   Durham Andrew A   Hennig Branwen J W BJ   Hellier Simon S   Knapp Susanne S   Wright Mark M   Chiaramonte Maria M   Bell John I JI   Graves Mary M   Whittle Hilton C HC   Thomas Howard C HC   Thursz Mark R MR   Hill Adrian V S AV  

Proceedings of the National Academy of Sciences of the United States of America 20060606 24

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 chromos  ...[more]

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