Letter abstract
Nature Genetics 41, 1100 - 1104 (2009)
Published online: 13 September 2009 | doi:10.1038/ng.447
IL28B is associated with response to chronic hepatitis C interferon-
and ribavirin therapy
Vijayaprakash Suppiah1,2, Max Moldovan3, Golo Ahlenstiel4, Thomas Berg5, Martin Weltman6, Maria Lorena Abate7, Margaret Bassendine8, Ulrich Spengler4, Gregory J Dore9,10, Elizabeth Powell11,12, Stephen Riordan13, David Sheridan8, Antonina Smedile7, Vincenzo Fragomeli6, Tobias Müller5, Melanie Bahlo3, Graeme J Stewart2, David R Booth2 & Jacob George1 for the Hepatitis C Study14
Hepatitis C virus (HCV) infects 3% of the world's population. Treatment of chronic HCV consists of a combination of PEGylated interferon-
(PEG-IFN-) and ribavirin (RBV). To identify genetic variants associated with HCV treatment response, we conducted a genome-wide association study of sustained virological response (SVR) to PEG-IFN-/RBV combination therapy in 293 Australian individuals with genotype 1 chronic hepatitis C, with validation in an independent replication cohort consisting of 555 individuals. We report an association to SVR within the gene region encoding interleukin 28B (IL28B, also called IFN
3; rs8099917 combined P = 9.25 
10-9, OR = 1.98, 95% CI = 1.57–2.52). IL28B contributes to viral resistance and is known to be upregulated by interferons and by RNA virus infection. These data suggest that host genetics may be useful for the prediction of drug response, and they also support the investigation of the role of IL28B in the treatment of HCV and in other diseases treated with IFN-.
- Storr Liver Unit, Westmead Millennium Institute, University of Sydney, Sydney, Australia.
- Institute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, Australia.
- The Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Victoria, Australia.
- Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Strasse, Bonn, Germany.
- Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin, Germany.
- Department of Gastroenterology and Hepatology, Nepean Hospital, Penrith, Sydney, Australia.
- University of Turin, Department of Internal Medicine, Liver Physiopathology Lab, Torino, Italy.
- Liver Research Group, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, UK.
- National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia.
- St. Vincent's Hospital, Sydney, Australia.
- Princess Alexandra Hospital, Department of Gastroenterology and Hepatology, Woolloongabba, Queensland, Australia.
- The University of Queensland, School of Medicine, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia.
- Gastrointestinal and Liver Unit, Prince of Wales Hospital and University of New South Wales, Sydney, Australia.
- A full list of members is provided in the Supplementary Note.
Correspondence to: e-mail: j.george@usyd.edu.au
