Letter abstract
Nature Genetics 41, 1105 - 1109 (2009)
Published online: 13 September 2009 | doi:10.1038/ng.449
Genome-wide association of IL28B with response to pegylated interferon-
and ribavirin therapy for chronic hepatitis C
Yasuhito Tanaka1,18, Nao Nishida2,18, Masaya Sugiyama1, Masayuki Kurosaki3, Kentaro Matsuura1, Naoya Sakamoto4, Mina Nakagawa4, Masaaki Korenaga5, Keisuke Hino5, Shuhei Hige6, Yoshito Ito7, Eiji Mita8, Eiji Tanaka9, Satoshi Mochida10, Yoshikazu Murawaki11, Masao Honda12, Akito Sakai12, Yoichi Hiasa13, Shuhei Nishiguchi14, Asako Koike15, Isao Sakaida16, Masatoshi Imamura17, Kiyoaki Ito17, Koji Yano17, Naohiko Masaki17, Fuminaka Sugauchi1, Namiki Izumi3, Katsushi Tokunaga2 & Masashi Mizokami1,17
The recommended treatment for patients with chronic hepatitis C, pegylated interferon-
(PEG-IFN-) plus ribavirin (RBV), does not provide sustained virologic response (SVR) in all patients. We report a genome-wide association study (GWAS) to null virological response (NVR) in the treatment of patients with hepatitis C virus (HCV) genotype 1 within a Japanese population. We found two SNPs near the gene IL28B on chromosome 19 to be strongly associated with NVR (rs12980275, P = 1.93 
10-13, and rs8099917, 3.11 10-15). We replicated these associations in an independent cohort (combined P values, 2.84 10-27 (OR = 17.7; 95% CI = 10.0–31.3) and 2.68 10-32 (OR = 27.1; 95% CI = 14.6–50.3), respectively). Compared to NVR, these SNPs were also associated with SVR (rs12980275, P = 3.99 10-24, and rs8099917, P = 1.11 10-27). In further fine mapping of the region, seven SNPs (rs8105790, rs11881222, rs8103142, rs28416813, rs4803219, rs8099917 and rs7248668) located in the IL28B region showed the most significant associations (P = 5.52 10-28–2.68 10-32; OR = 22.3–27.1). Real-time quantitative PCR assays in peripheral blood mononuclear cells showed lower IL28B expression levels in individuals carrying the minor alleles (P = 0.015).
- Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
- Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
- Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
- Division of Hepatology and Pancreatology, Kawasaki Medical College, 577 Matsushima, Kurashiki, Japan.
- Department of Internal Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
- National Hospital Organization Osaka National Hospital, Osaka, Japan.
- Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
- Division of Gastroenterology and Hepatology, Internal Medicine, Saitama Medical University, Saitama, Japan.
- Second department of Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
- Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.
- Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
- Central Research Laboratory, Hitachi Ltd., Kokubunji, Japan.
- Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
- Research Center for Hepatitis and Immunology, International Medical Center of Japan Konodai Hospital, Ichikawa, Japan.
- These authors contributed equally to this work.
Correspondence to: Masashi Mizokami1,17 e-mail: mmizokami@imcjk2.hosp.go.jp
