Liao Dan, Hou Shengping, Zhang Jun, Fang Jing, Liu Yunjia, Bai Lin, Cao Qingfeng, Kijlstra Aize, Yang Peizeng
The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, China.
University Eye Clinic Maastricht, Maastricht, The Netherlands.
Sci Rep. 2015 Apr 15;5:9511. doi: 10.1038/srep09511.
This study aimed to investigate the role of genetic variants including single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) of TBX21, GATA3, Rorc and Foxp3 genes in Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population. Genotyping of 25 SNPs was performed by iPLEX system (Sequenom) or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). TaqMan real time PCR was used to assess CNVs. The expression of Rorc and Foxp3 were examined by real-time PCR and cytokine production was measured by ELISA. High Rorc CNV was associated with the susceptibility to BD (P = 8.99 × 10(-8), OR = 3.0), and low Foxp3 CNV predisposed to BD in female patients (P = 1.92 × 10(-5), OR = 3.1). CNVs for the investigated genes were not altered in VKH syndrome. Further functional studies demonstrated that the relative mRNA expression levels of Rorc were increased in individuals with high Rorc copy number, but not for Foxp3. Increased production of IL-1β and IL-6 was found in individuals carrying a high CNV of Rorc. Our study showed that high CNVs of Rorc and low CNVs of Foxp3 confer risk for BD but not for VKH syndrome. The tested 25 SNPs in TBX21, GATA3, Rorc and Foxp3 did not associate with BD and VKH syndrome.
本研究旨在探讨TBX21、GATA3、Rorc和Foxp3基因的单核苷酸多态性（SNP）和拷贝数变异（CNV）等基因变异在中国汉族人群白塞病（BD）和Vogt-小柳原田（VKH）综合征中的作用。采用iPLEX系统（Sequenom）或聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对25个SNP进行基因分型。运用TaqMan实时PCR评估CNV。通过实时PCR检测Rorc和Foxp3的表达，并采用酶联免疫吸附测定（ELISA）检测细胞因子的产生。高Rorc CNV与BD易感性相关（P = 8.99 × 10(-8)，OR = 3.0），低Foxp3 CNV使女性BD患者易患该病（P = 1.92 × 10(-5)，OR = 3.1）。所研究基因的CNV在VKH综合征中未发生改变。进一步的功能研究表明，Rorc拷贝数高的个体中Rorc的相对mRNA表达水平升高，但Foxp3并非如此。在携带高Rorc CNV的个体中发现IL-1β和IL-6的产生增加。我们的研究表明，高Rorc CNV和低Foxp3 CNV会增加BD的发病风险，但不会增加VKH综合征的发病风险。TBX21、GATA3、Rorc和Foxp3中检测的25个SNP与BD和VKH综合征无关。
