A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians

被引：435

作者：

Kamatani, Yoichiro ^{[1
,2
]}

Wattanapokayakit, Sukanya ^{[3
]}

Ochi, Hidenori ^{[4
,5
]}

Kawaguchi, Takahisa ^{[4
]}

Takahashi, Atsushi ^{[4
]}

Hosono, Naoya ^{[4
]}

Kubo, Michiaki ^{[4
]}

Tsunoda, Tatsuhiko ^{[4
]}

Kamatani, Naoyuki ^{[4
]}

Kumada, Hiromitsu ^{[6
]}

Puseenam, Aekkachai ^{[7
]}

Sura, Thanyachai ^{[7
]}

Daigo, Yataro ^{[1
,2
]}

Chayama, Kazuaki ^{[4
,5
]}

Chantratita, Wasun ^{[8
]}

Nakamura, Yusuke ^{[1
,4
]}

Matsuda, Koichi ^{[1
]}

机构：

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

[2] Univ Tokyo, Dept Med Genome Sci, Grad Sch Frontier Sci, Tokyo, Japan

[3] Minist Publ Hlth, Dept Med Sci, Natl Inst Hlth, Med Genet Sect, Nonthaburi, Thailand

[4] RIKEN, Ctr Genom Med, Kanagawa, Japan

[5] Hiroshima Univ, Grad Sch Biomed Sci, Programs Biomed Res, Dept Med & Mol Sci,Div Frontier Med Sci, Hiroshima, Japan

[6] Toranomon Gen Hosp, Dept Hepatol, Tokyo, Japan

[7] Mahidol Univ, Ramathidi Hosp, Fac Med, Dept Med, Bangkok 10700, Thailand

[8] Mahidol Univ, Ramathidi Hosp, Fac Med, Virol & Mol Microbiol Unit,Dept Pathol, Bangkok 10700, Thailand

来源：

NATURE GENETICS | 2009年 / 41卷 / 05期

关键词：

VIRUS-INFECTION; SURFACE-ANTIGEN; RECEPTOR GENE; SUSCEPTIBILITY; POLYMORPHISMS; POPULATION; ALLELES; MARKERS;

D O I：

10.1038/ng.348

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Chronic hepatitis B is a serious infectious liver disease that often progresses to liver cirrhosis and hepatocellular carcinoma; however, clinical outcomes after viral exposure vary enormously among individuals(1). Through a two-stage genome-wide association study using 786 Japanese chronic hepatitis B cases and 2,201 controls, we identified a significant association of chronic hepatitis B with 11 SNPs in a region including HLA-DPA1 and HLA-DPB1. We validated these associations by genotyping two SNPs from the region in three additional Japanese and Thai cohorts consisting of 1,300 cases and 2,100 controls (combined P = 6.34 x 10(-39) and 2.31 x 10(-38), OR = 0.57 and 0.56, respectively). Subsequent analyses revealed risk haplotypes (HLA-DPA1*0202-DPB1*0501 and HLA-DPA1*0202-DPB1*0301, OR = 1.45 and 2.31, respectively) and protective haplotypes (HLA-DPA1*0103-DPB1*0402 and HLA-DPA1*0103-DPB1*0401, OR = 0.52 and 0.57, respectively). Our findings show that genetic variants in the HLA-DP locus are strongly associated with risk of persistent infection with hepatitis B virus.

引用

页码：591 / 595

页数：5

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