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PMID: 19749758 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy.

Nature genetics ·Vol. 41 ·No. 10 ·2009-10-00 ·Pages 1100-4

Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, Bassendine M, Spengler U, Dore GJ, Powell E, Riordan S, Sheridan D, Smedile A, Fragomeli V, Müller T, Bahlo M, Stewart GJ, Booth DR, George J

Abstract

Hepatitis C virus (HCV) infects 3% of the world's population. Treatment of chronic HCV consists of a combination of PEGylated interferon-alpha (PEG-IFN-alpha) and ribavirin (RBV). To identify genetic variants associated with HCV treatment response, we conducted a genome-wide association study of sustained virological response (SVR) to PEG-IFN-alpha/RBV combination therapy in 293 Australian individuals with genotype 1 chronic hepatitis C, with validation in an independent replication cohort consisting of 555 individuals. We report an association to SVR within the gene region encoding interleukin 28B (IL28B, also called IFNlambda3; rs8099917 combined P = 9.25 x 10(-9), OR = 1.98, 95% CI = 1.57-2.52). IL28B contributes to viral resistance and is known to be upregulated by interferons and by RNA virus infection. These data suggest that host genetics may be useful for the prediction of drug response, and they also support the investigation of the role of IL28B in the treatment of HCV and in other diseases treated with IFN-alpha.

MeSH Terms
Adult Antiviral Agents/therapeutic use Australia Drug Therapy, Combination Female Gene Expression Regulation Genome-Wide Association Study Genotype Hepatitis C, Chronic/drug therapy,genetics,virology Humans Interferon-alpha/therapeutic use Interferons Interleukins/genetics Male Middle Aged Polyethylene Glycols/therapeutic use Polymorphism, Single Nucleotide Ribavirin/therapeutic use Treatment Outcome
Chemicals
Antiviral Agents IFNL3 protein, human Interferon-alpha Interleukins Polyethylene Glycols Ribavirin Interferons
Authors & Affiliations
19 authors, click to expand affiliations / ORCID
Suppiah Vijayaprakash
Storr Liver Unit, University of Sydney, Sydney, Australia.
Moldovan Max
Ahlenstiel Golo
Berg Thomas
Weltman Martin
Abate Maria Lorena
Bassendine Margaret
Spengler Ulrich
Dore Gregory J
Powell Elizabeth
Riordan Stephen
Sheridan David
Smedile Antonina
Fragomeli Vincenzo
Müller Tobias
Bahlo Melanie
Stewart Graeme J
Booth David R
George Jacob
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.447
Published
2009-10-00
Epub
2009-00-13
Pages
1100-4
Language
English
Region
United States
NLM ID
9216904
Subset
IM
Grants
Medical Research Council · G0502028 · United Kingdom
Corrections
CommentIn
PMID: 19749756
CommentIn
PMID: 20136353
CommentIn
PMID: 20175968
External Links
PubMed source DOI: 10.1038/ng.447 View journal details
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