A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians
A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians
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DOI：
10.1038/ng.348
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发表时间：
2009-05-01
期刊：
影响因子：
30.8
通讯作者：
Matsuda, Koichi
中科院分区：
文献类型：
--
作者：
Kamatani, Yoichiro;Wattanapokayakit, Sukanya;Matsuda, Koichi
慢性乙型肝炎是一种严重的传染性肝病，常发展为肝硬化和肝细胞癌；然而，病毒暴露后的临床结果在个体之间差异很大(1)。通过对786名日本慢性乙型肝炎患者和2201名对照组进行的两阶段全基因组关联研究，我们发现慢性乙型肝炎与HLA-DPA1和HLA-DPB1区域的11个snp存在显著关联。我们通过在另外三个日本和泰国队列中对来自该地区的两个snp进行基因分型来验证这些关联，这些队列包括1300例病例和2100例对照（P = 6.34 × 10（-39）和2.31 × 10(-38)， OR分别= 0.57和0.56）。随后的分析发现了风险单倍型（HLA-DPA1*0202-DPB1*0501和HLA-DPA1*0202-DPB1*0301， OR分别为1.45和2.31）和保护单倍型（HLA-DPA1*0103-DPB1*0402和HLA-DPA1*0103-DPB1*0401， OR分别为0.52和0.57）。我们的研究结果表明，HLA-DP基因座的遗传变异与乙型肝炎病毒持续感染的风险密切相关。
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.