作者
Shengping Hou,Liping Du,Bo Lei,Chi Pui Pang,Meifen Zhang,Wenjuan Zhuang,Minglian Zhang,Lulin Huang,Bo Gong,Meilin Wang,Qí Zhāng,Ke Hu,Qingyun Zhou,Jian Qi,Chaokui Wang,Yuan Tian,Zi Ye,Liang Liang,Hongsong Yu,Hong Li,Yan Zhou,Qingfeng Cao,Yunjia Liu,Lin Bai,Dan Liao,Aize Kijlstra,Jianfeng Xu,Zhenglin Yang,Peizeng Yang
摘要
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 × 10(-21), odds ratio (OR) = 1.82; ADO-ZNF365-EGR2, rs442309, P(combined) = 2.97 × 10(-11), OR = 1.37; and HLA-DRB1/DQA1, rs3021304, P(combined) = 1.26 × 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.