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Abstract Details
IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction
Bibert S, Roger T, Calandra T, Bochud M, Cerny A, Semmo N, Duong FH, Gerlach T, Malinverni R, Moradpour D, Negro F, Müllhaupt B, Bochud PY; Swiss Hepatitis C Cohort Study. J Exp Med. 2013 Jun 3;210(6):1109-16. doi: 10.1084/jem.20130012. Epub 2013 May 27.
Source
Infectious Diseases Service and 2 Division of Gastroenterology, Department of Medicine and Hepatology, University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.
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.