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

Bibert, Stéphanie; Roger, Thierry; Calandra, Thierry; Bochud, Murielle; Cerny, Andreas; Semmo, Nasser; Duong, François H. T.; Gerlach, Tilman; Malinverni, Raffaele; Moradpour, Darius; Negro, Francesco; Müllhaupt, Beat; Bochud, Pierre-Yves; Swiss Hepatitis C Cohort Study, the; Dufour, Jean-François (2013). IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction. Journal of experimental medicine, 210(6), pp. 1109-1116. Rockefeller University Press 10.1084/jem.20130012

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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.

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