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IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction

Roger, Thierry
Calandra, Thierry
Cerny, Andreas
Semmo, Nasser
Duong, François H T
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Published in Journal of Experimental Medicine. 2013, vol. 210, no. 6, p. 1109-16
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.
PMID: 23712427
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Research group Etudes et traitement de l'hépatite C et B (554)
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BIBERT, Stéphanie et al. IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction. In: Journal of Experimental Medicine, 2013, vol. 210, n° 6, p. 1109-16. https://archive-ouverte.unige.ch/unige:29307

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Deposited on : 2013-08-14

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