title: 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.affiliation: Storr Liver Unit, University of Sydney, Sydney, Australia.
authors.forename: Vijayaprakash
authors.initials: V
authors.lastname: Suppiah
authors.forename: Max
authors.initials: M
authors.lastname: Moldovan
authors.forename: Golo
authors.initials: G
authors.lastname: Ahlenstiel
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Martin
authors.initials: M
authors.lastname: Weltman
authors.forename: Maria Lorena
authors.initials: ML
authors.lastname: Abate
authors.forename: Margaret
authors.initials: M
authors.lastname: Bassendine
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Powell
authors.forename: Stephen
authors.initials: S
authors.lastname: Riordan
authors.forename: David
authors.initials: D
authors.lastname: Sheridan
authors.forename: Antonina
authors.initials: A
authors.lastname: Smedile
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Fragomeli
authors.forename: Tobias
authors.initials: T
authors.lastname: Müller
authors.forename: Melanie
authors.initials: M
authors.lastname: Bahlo
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Stewart
authors.forename: David R
authors.initials: DR
authors.lastname: Booth
authors.forename: Jacob
authors.initials: J
authors.lastname: George
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001315:Australia; D004359:Drug Therapy, Combination; D005260:Female; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda