Class II cytokine receptor gene cluster is a major locus for hepatitis B persistence.
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.
Frodsham
Angela J
AJ
The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.
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
D006528:Carcinoma, Hepatocellular / Q000821:virology; D002353:Carrier State; D002460:Cell Line; D005714:Gambia; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D019694:Hepatitis B, Chronic / Q000235:genetics / Q000276:immunology; D006801:Humans; D015810:Linkage Disequilibrium; D008113:Liver Neoplasms / Q000821:virology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D011110:Polymorphism, Genetic; D053633:Receptor, Interferon alpha-beta; D018121:Receptors, Cytokine; D017471:Receptors, Interferon / Q000235:genetics* / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics* / Q000378:metabolism; D053701:Receptors, Interleukin-10; D017422:Sequence Analysis, DNA; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D005819:Genetic Markers; D008565:Membrane Proteins; D018121:Receptors, Cytokine; D017471:Receptors, Interferon; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D014409:Tumor Necrosis Factor-alpha; D053633:Receptor, Interferon alpha-beta