Promoter Hypermethylation of GATA3, IL-4, and TGF-β Confers Susceptibility to Vogt-Koyanagi-Harada Disease in Han Chinese

作者：Zhu, Yunyun; Yu, Hongsong; Qiu, Yiguo; Ye, Zi; Su, Wencheng; Deng, Jing; Cao, Qingfeng; Yuan, Gangxiang; Kijlstra, Aize; Yang, Peizeng^*

来源：Investigative Ophthalmology & Visual Science, 2017, 58(3): 1529-1536.

DOI：10.1167/iovs.16-21188

• Vogt-Koyanagi-Harada disease
• DNA methylation
• CD4(+) T cell
• autoimmune diseases

PURPOSE. We investigated the role of promoter methylation of transcriptional and inflammatory factors, including TBX21, GATA3, ROR gamma t, FOXP3, IFN-gamma, IL-4, IL-17A, and TGF-beta in the development of Vogt-Koyanagi-Harada (VKH) disease. @@@ METHODS. The promoter methylation levels were detected by the Sequenom MassARRAY system in CD4(+) T cells that were separated from 20 healthy individuals and 32 VKH patients (20 in the active stage without medication, 12 in inactive stage with medication). The mRNA expression level of GATA3, IL-4, and TGF-b in CD4(+) T cells was analyzed by real-time RT-PCR. @@@ RESULTS. The promoter methylation levels of GATA3, IL-4, and TGF-b were significantly higher in active VKH patients than in healthy individuals (P < 0.05). A decreased mRNA expression of GATA3 and TGF-b was found in active VKH patients, which was correlated negatively with the DNA methylation of these factors. Treatment with systemic corticosteroid and cyclosporin A (CsA) decreased the methylation level of GATA3 and TGF-b in association with an increased mRNA expression of molecules and reduced disease activity. @@@ CONCLUSIONS. Our findings suggest that promoter hypermethylation of GATA3 and TGF-b in CD4(+) T cells confers risk to VKH disease in Han Chinese.

• 出版日期2017-3
• 单位重庆医科大学