Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma

被引：308

作者：

Kumar, Vinod ^{[1
,2
]}

Kato, Naoya ^{[3
]}

Urabe, Yuji ^{[1
]}

Takahashi, Atsushi ^{[2
]}

Muroyama, Ryosuke ^{[3
]}

Hosono, Naoya ^{[2
]}

Otsuka, Motoyuki ^{[4
]}

Tateishi, Ryosuke ^{[4
]}

Omata, Masao ^{[4
]}

Nakagawa, Hidewaki ^{[2
]}

Koike, Kazuhiko ^{[4
]}

Kamatani, Naoyuki ^{[2
]}

Kubo, Michiaki ^{[2
]}

Nakamura, Yusuke ^{[1
,2
]}

Matsuda, Koichi ^{[1
]}

机构：

[1] Univ Tokyo, Lab Mol Med, Ctr Human Genome, Inst Med Sci, Tokyo, Japan

[2] Inst Phys & Chem Res RIKEN, Ctr Genom Med, Kanagawa, Japan

[3] Univ Tokyo, Unit Dis Control Genome Med, Inst Med Sci, Tokyo, Japan

[4] Univ Tokyo, Dept Gastroenterol, Grad Sch Med, Tokyo, Japan

来源：

NATURE GENETICS | 2011年 / 43卷 / 05期

关键词：

HEPATITIS-C VIRUS; MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I; T-CELLS; GENETIC-VARIATION; HAPLOTYPE MAP; CHAIN-A; MICA; MHC; EXPRESSION;

D O I：

10.1038/ng.809

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

To identify the genetic susceptibility factor(s) for hepatitis C virus-induced hepatocellular carcinoma (HCV-induced HCC), we conducted a genome-wide association study using 432,703 autosomal SNPs in 721 individuals with HCV-induced HCC (cases) and 2,890 HCV-negative controls of Japanese origin. Eight SNPs that showed possible association (P < 1 x 10(-5)) in the genome-wide association study were further genotyped in 673 cases and 2,596 controls. We found a previously unidentified locus in the 5' flanking region of MICA on 6p21.33 (rs2596542, P-combined = 4.21 x 10(-13), odds ratio = 1.39) to be strongly associated with HCV-induced HCC. Subsequent analyses using individuals with chronic hepatitis C (CHC) indicated that this SNP is not associated with CHC susceptibility (P = 0.61) but is significantly associated with progression from CHC to HCC (P = 3.13 x 10(-8)). We also found that the risk allele of rs2596542 was associated with lower soluble MICA protein levels in individuals with HCV-induced HCC (P = 1.38 x 10(-13)).

引用

页码：455 / +

页数：5

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