Genome-wide association analysis of Vogt-Koyanagi-Harada syndrome identifies two new susceptibility loci at 1p31.2 and 10q21.3
Genome-wide association analysis of Vogt-Koyanagi-Harada syndrome identifies two new susceptibility loci at 1p31.2 and 10q21.3
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Vogt-Koyanagi-Harada 综合征的全基因组关联分析确定了 1p31.2 和 10q21.3 处的两个新的易感性位点。
DOI：
10.1038/ng.3061
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发表时间：
2014-09-01
期刊：
影响因子：
30.8
通讯作者：
Yang, Peizeng
中科院分区：
文献类型：
--
作者：
Hou, Shengping;Du, Liping;Yang, Peizeng
为了确定Vogt-Koyanagi-Harada（VKH）综合征的新遗传危险因素，我们对774例病例和2,009例对照的2,208,258个SNP进行了全基因组关联研究，并对415例病例和2,006例对照以及349例病例和1,588例对照进行了随访。我们确定了三个与VKH综合征易感性相关的基因座ADO-ZNF 365-EGR2，rs442309，P-combined = 2.97 x 10（-11），OR = 1.37; HLA-DRB 1/DQA 1，rs3021304，P-组合= 1.26 × 10 - 118，OR = 2.97）。5个非HLA基因均在人虹膜组织中表达。IL 23 R在睫状体中也有表达，EGFR 2在睫状体和脉络膜中也有表达。IL 23 R启动子区rs 117633859的风险G等位基因在基于细胞的报告基因测定中表现出低转录激活，并与人外周血单核细胞中IL 23 R mRNA表达减少相关。
To identify new genetic risk factors for Vogt-Koyanagi-Harada (VKH) syndrome, we conducted a genome-wide association study of 2,208,258 SNPs in 774 cases and 2,009 controls with follow-up in a collection of 415 cases and 2,006 controls and a further collection of 349 cases and 1,588 controls from a Han Chinese population. We identified three loci associated with VKH syndrome susceptibility (IL23R-C1orf141, rs117633859, P-combined = 3.42 x 10(-21), odds ratio (OR) = 1.82; ADO-ZNF365-EGR2, rs442309, P-combined = 2.97 x 10(-11), OR = 1.37; and HLA-DRB1/DQA1, rs3021304, P-combined = 1.26 x 10(-118), OR = 2.97). The five non-HLA genes were all expressed in human iris tissue. IL23R was also expressed in the ciliary body, and EGR2 was expressed in the ciliary body and choroid. The risk G allele of rs117633859 in the promoter region of IL23R exhibited low transcriptional activation in a cell-based reporter assay and was associated with diminished IL23R mRNA expression in human peripheral blood mononuclear cells.