Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 210, Issue 6, Pages 1109-1116Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20130012
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Funding
- Swiss National Foundation [32003B-127613, 324730-144054]
- Leenaards Foundation
- Santos-Suarez Foundation
- Loterie Romande
- European Commission under the Health Cooperation Work Program of the seventh Framework Program [260844]
- Swiss National Science Foundation [3347C0-108782/1]
- Swiss Federal Office for Education and Sciences [03.0599]
- European Commission [LSHM-CT-2004-503359]
- Swiss National Science Foundation (SNF) [324730_144054, 32003B_127613] Funding Source: Swiss National Science Foundation (SNF)
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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-gamma-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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