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

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.
Authors	Vijayaprakash Suppiah, Max Moldovan, Golo Ahlenstiel, Thomas Berg, Martin Weltman, Maria Lorena Abate, Margaret Bassendine, Ulrich Spengler, Gregory J Dore, Elizabeth Powell, Stephen Riordan, David Sheridan, Antonina Smedile, Vincenzo Fragomeli, Tobias Müller, Melanie Bahlo, Graeme J Stewart, David R Booth, Jacob George
Journal	Nature genetics (Nat Genet) Vol. 41 Issue 10 Pg. 1100-4 (Oct 2009) ISSN: 1546-1718 [Electronic] United States
PMID	19749758 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antiviral Agents IFNL3 protein, human Interferon-alpha Interleukins Polyethylene Glycols Ribavirin Interferons
Topics	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

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