一项全基因组关联研究确定了亚洲人中与慢性乙型肝炎相关的HLA-DP基因座变异。
A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians.
作者信息
Kamatani Yoichiro, Wattanapokayakit Sukanya, Ochi Hidenori, Kawaguchi Takahisa, Takahashi Atsushi, Hosono Naoya, Kubo Michiaki, Tsunoda Tatsuhiko, Kamatani Naoyuki, Kumada Hiromitsu, Puseenam Aekkachai, Sura Thanyachai, Daigo Yataro, Chayama Kazuaki, Chantratita Wasun, Nakamura Yusuke, Matsuda Koichi
机构信息
Human Genome Center, Institute of Medical Science, the University of Tokyo, Japan.
出版信息
Nat Genet. 2009 May;41(5):591-5. doi: 10.1038/ng.348. Epub 2009 Apr 6.
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. 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.
慢性乙型肝炎是一种严重的传染性肝病，常进展为肝硬化和肝细胞癌；然而，病毒暴露后的临床结局在个体间差异极大。通过一项两阶段全基因组关联研究，我们对786例日本慢性乙型肝炎病例和2201例对照进行了研究，发现慢性乙型肝炎与包括HLA - DPA1和HLA - DPB1在内的一个区域中的11个单核苷酸多态性（SNP）存在显著关联。我们通过对另外三个由1300例病例和2100例对照组成的日本和泰国队列中的该区域的两个SNP进行基因分型，验证了这些关联（合并P值 = 6.34 x 10(-39) 和2.31 x 10(-38)，优势比分别为0.57和0.56）。随后的分析揭示了风险单倍型（HLA - DPA1()0202 - DPB1()0501和HLA - DPA1()0202 - DPB1()0301，优势比分别为1.45和2.31）和保护性单倍型（HLA - DPA1()0103 - DPB1()0402和HLA - DPA1()0103 - DPB1()0401，优势比分别为0.52和0.57）。我们的研究结果表明，HLA - DP基因座中的基因变异与乙型肝炎病毒持续感染风险密切相关。
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