Cao Shuang, Chee Soon Phaik, Yu Hyeong Gon, Sukavatcharin Somsiri, Wu Lili, Kijlstra Aize, Hou Shengping, Yang Peizeng
Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China Chongqing Eye Institute, Chongqing, P. R. China Chongqing Key Laboratory of Ophthalmology, Chongqing, P. R. China.
Singapore National Eye Centre, Singapore, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Singapore Eye Research Institute, Singapore, Singapore Department of Ophthalmology and Visual Sciences, Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.
Br J Ophthalmol. 2016 Mar;100(3):436-42. doi: 10.1136/bjophthalmol-2015-307366. Epub 2015 Dec 1.
We performed a multistage genome-wide association study of Vogt-Koyanagi-Harada (VKH) syndrome in a Han Chinese population and identified two novel non-human leukocyte antigen candidate regions previously. The aim of the study was to replicate the association of IL23R-C1orf141 and ADO-ZNF365-EGR2 with VKH syndrome in four sets of multinational populations in Asia.
We conducted a candidate genes association study involving 185 patients with VKH syndrome and 287 normal controls from Han Chinese Singaporeans, non-Han Chinese, Thais and Koreans. Genotyping of 16 single nucleotide polymorphisms (SNPs) within IL23R-C1orf141 and ADO-ZNF365-EGR2 loci was performed using the Sequenom MassARRAY system or by Taqman SNP assays.
Eight SNPs in IL23R-Clorf141 showed an association with VKH syndrome only in Han Chinese Singaporeans (p=8.49×10(-5) to 1.02×10(-3), pcorrection=1.69×10(-4) to 2.04×10(-3)) but not in the other groups tested. One SNP rs1884444 in IL23R-Clorf141 was found to be weakly associated with VKH syndrome in the Han Chinese Singaporeans, but significance was lost following Bonferroni correction for multiple comparisons. Five SNPs in ADO-ZNF365-EGR2 were found to be associated with VKH syndrome in Thai patients with VKH (p=0.014, pc=0.028) but not in the other three ethnic groups tested.
This study confirmed the genetic associations between SNPs in IL23R-C1orf141 and VKH syndrome in Han Chinese Singaporeans but not in other Asian populations. In addition, we also successfully replicated the association of VKH syndrome with ADO-ZNF365-EGR2 in a Thai population.
我们在汉族人群中开展了一项多阶段的葡萄膜炎-小柳原田综合征（VKH）全基因组关联研究，并在此前鉴定出两个新的非人类白细胞抗原候选区域。本研究的目的是在四组亚洲多国人群中重复白细胞介素23受体-1号染色体开放阅读框141（IL23R-C1orf141）和腺苷脱氨酶锌指蛋白365-早期生长反应因子2（ADO-ZNF365-EGR2）与VKH综合征的关联性。
我们开展了一项候选基因关联研究，纳入了来自新加坡华裔、非华裔、泰国人和韩国人的185例VKH综合征患者和287名正常对照。使用Sequenom MassARRAY系统或Taqman单核苷酸多态性（SNP）检测法对IL23R-C1orf141和ADO-ZNF365-EGR2基因座内的16个SNP进行基因分型。
IL23R-Clorf141中的8个SNP仅在新加坡华裔中显示与VKH综合征有关联（p=8.49×10⁻⁵至1.02×10⁻³，校正p值=1.69×10⁻⁴至2.04×10⁻³），而在其他受试组中未显示关联。发现IL23R-Clorf141中的一个SNP rs1884444在新加坡华裔中与VKH综合征存在弱关联，但在进行多重比较的Bonferroni校正后显著性消失。在泰国VKH综合征患者中，发现ADO-ZNF365-EGR2中的5个SNP与VKH综合征有关联（p=0.014，校正p值=0.028），但在其他三个受试种族中未显示关联。
本研究证实了IL23R-C1orf141中的SNP与新加坡华裔的VKH综合征之间存在遗传关联，但在其他亚洲人群中未得到证实。此外，我们还成功在泰国人群中重复了VKH综合征与ADO-ZNF365-EGR2的关联。
