title: IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction.
abstract: Approximately 3% of the world population is chronically infected with the hepatitis C virus (HCV), with potential development of cirrhosis and hepatocellular carcinoma. Despite the availability of new antiviral agents, treatment remains suboptimal. Genome-wide association studies (GWAS) identified rs12979860, a polymorphism nearby IL28B, as an important predictor of HCV clearance. We report the identification of a novel TT/-G polymorphism in the CpG region upstream of IL28B, which is a better predictor of HCV clearance than rs12979860. By using peripheral blood mononuclear cells (PBMCs) from individuals carrying different allelic combinations of the TT/-G and rs12979860 polymorphisms, we show that induction of IL28B and IFN-γ-inducible protein 10 (IP-10) mRNA relies on TT/-G, but not rs12979860, making TT/-G the only functional variant identified so far. This novel step in understanding the genetic regulation of IL28B may have important implications for clinical practice, as the use of TT/G genotyping instead of rs12979860 would improve patient management.
authors.affiliation: Infectious Diseases Service, Department of Medicine and Hepatology, University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bibert
authors.forename: Thierry
authors.initials: T
authors.lastname: Roger
authors.forename: Thierry
authors.initials: T
authors.lastname: Calandra
authors.forename: Murielle
authors.initials: M
authors.lastname: Bochud
authors.forename: Andreas
authors.initials: A
authors.lastname: Cerny
authors.forename: Nasser
authors.initials: N
authors.lastname: Semmo
authors.forename: François H T
authors.initials: FH
authors.lastname: Duong
authors.forename: Tilman
authors.initials: T
authors.lastname: Gerlach
authors.forename: Raffaele
authors.initials: R
authors.lastname: Malinverni
authors.forename: Darius
authors.initials: D
authors.lastname: Moradpour
authors.forename: Francesco
authors.initials: F
authors.lastname: Negro
authors.forename: Beat
authors.initials: B
authors.lastname: Müllhaupt
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Bochud
mesh_terms: D000483:Alleles; D054357:Chemokine CXCL10 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D005838:Genotype; D016174:Hepacivirus / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007372:Interferons; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics; D000095022:Interferon Lambda
chemical_list: D054357:Chemokine CXCL10; D007371:Interferon-gamma; D007372:Interferons; D007378:Interleukins; D012333:RNA, Messenger; C114753:CXCL10 protein, human; C000624353:interferon-lambda, human; D000095022:Interferon Lambda