Genome-wide Association of IL28B with Response to Pegylated Interferon-alpha and Ribavirin Therapy for Chronic Hepatitis C

Overview

Journal Nat Genet

Specialty Genetics

Date 2009 Sep 15

PMID 19749757

Citations 849

Authors

Yasuhito Tanaka

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

Affiliations

Soon will be listed here.

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).

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