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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 J.W. Hennig
  • , Simon Hellier
  • , Susanne Knapp
  • , Mark Wright
  • , Maria Chiaramonte
  • , John I. Bell
  • , Mary Graves
  • , Hilton C. Whittle
  • , Howard C. Thomas
  • , Mark R. Thursz*
  • , Adrian V.S. Hill
  • *Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

101 Citations (Scopus)

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 ≈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 IIFN receptor gene, IFN-AR2, and the IL-10RB gene that encodes a receptor chain for IL-10-related cytokines including the IFN-As, are associated with viral clearance (haplotype P value = 0.0003), and in vitro assays support functional roles for these variants in receptor signaling.

Original languageEnglish
Pages (from-to)9148-9153
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number24
DOIs
Publication statusPublished - 13 Jun 2006
Externally publishedYes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • Complex trait
  • IL-10
  • Interferon
  • Susceptibility
  • Virus

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