title: Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance.
abstract: Chronic infection with hepatitis C virus (HCV) affects 170 million people worldwide and is the leading cause of cirrhosis in North America. Although the recommended treatment for chronic infection involves a 48-week course of peginterferon-alpha-2b (PegIFN-alpha-2b) or -alpha-2a (PegIFN-alpha-2a) combined with ribavirin (RBV), it is well known that many patients will not be cured by treatment, and that patients of European ancestry have a significantly higher probability of being cured than patients of African ancestry. In addition to limited efficacy, treatment is often poorly tolerated because of side effects that prevent some patients from completing therapy. For these reasons, identification of the determinants of response to treatment is a high priority. Here we report that a genetic polymorphism near the IL28B gene, encoding interferon-lambda-3 (IFN-lambda-3), is associated with an approximately twofold change in response to treatment, both among patients of European ancestry (P = 1.06 x 10(-25)) and African-Americans (P = 2.06 x 10(-3)). Because the genotype leading to better response is in substantially greater frequency in European than African populations, this genetic polymorphism also explains approximately half of the difference in response rates between African-Americans and patients of European ancestry.
authors.affiliation: Institute for Genome Sciences & Policy, Center for Human Genome Variation, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Ge
authors.forename: Jacques
authors.initials: J
authors.lastname: Fellay
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: Jason S
authors.initials: JS
authors.lastname: Simon
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Shianna
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Urban
authors.forename: Erin L
authors.initials: EL
authors.lastname: Heinzen
authors.forename: Ping
authors.initials: P
authors.lastname: Qiu
authors.forename: Arthur H
authors.initials: AH
authors.lastname: Bertelsen
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Muir
authors.forename: Mark
authors.initials: M
authors.lastname: Sulkowski
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.forename: David B
authors.initials: DB
authors.lastname: Goldstein
mesh_terms: D001741:Black or African American / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002986:Clinical Trials as Topic; D005060:Europe / Q000208:ethnology; D005202:Asia, Eastern / Q000208:ethnology; D005787:Gene Frequency; D014644:Genetic Variation / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics* / Q000821:virology; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D010597:Pharmacogenetics; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011994:Recombinant Proteins; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b
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