| Literature DB >> 19749757 |
Yasuhito Tanaka1, Nao Nishida, Masaya Sugiyama, Masayuki Kurosaki, Kentaro Matsuura, Naoya Sakamoto, Mina Nakagawa, Masaaki Korenaga, Keisuke Hino, Shuhei Hige, Yoshito Ito, Eiji Mita, Eiji Tanaka, Satoshi Mochida, Yoshikazu Murawaki, Masao Honda, Akito Sakai, Yoichi Hiasa, Shuhei Nishiguchi, Asako Koike, Isao Sakaida, Masatoshi Imamura, Kiyoaki Ito, Koji Yano, Naohiko Masaki, Fuminaka Sugauchi, Namiki Izumi, Katsushi Tokunaga, Masashi Mizokami.
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).Entities:
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Year: 2009 PMID： 19749757 DOI： 10.1038/ng.449
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330