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- Title
Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C.
- Authors
Tanaka, Yasuhito; Nishida, Nao; Sugiyama, Masaya; Kurosaki, Masayuki; Matsuura, Kentaro; Sakamoto, Naoya; Nakagawa, Mina; Korenaga, Masaaki; Hino, Keisuke; Hige, Shuhei; Ito, Yoshito; Mita, Eiji; Tanaka, Eiji; Mochida, Satoshi; Murawaki, Yoshikazu; Honda, Masao; Sakai, Akito; Hiasa, Yoichi; Nishiguchi, Shuhei; Koike, Asako; Sakaida, Isao; Imamura, Masatoshi; Ito, Kiyoaki; Yano, Koji; Masaki, Naohiko; Sugauchi, Fuminaka; Izumi, Namiki; Tokunaga, Katsushi; Mizokami, Masashi
- Abstract
The recommended treatment for patients with chronic hepatitis C, pegylated interferon-alpha (PEG-IFN-alpha) 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 x 10(-13), and rs8099917, 3.11 x 10(-15)). We replicated these associations in an independent cohort (combined P values, 2.84 x 10(-27) (OR = 17.7; 95% CI = 10.0-31.3) and 2.68 x 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 x 10(-24), and rs8099917, P = 1.11 x 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 x 10(-28)-2.68 x 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).
- Publication
Nature genetics, 2009, Vol 41, Issue 10, p1105
- ISSN
1546-1718
- Publication type
Journal Article
- DOI
10.1038/ng.449