Aberrant DNA methylation of GATA binding protein 3 (GATA3), interleukin-4 (IL-4), and transforming growth factor-β (TGF-β) promoters in Behcet's disease

白塞氏病中GATA结合蛋白3 (GATA3)、白细胞介素-4 (IL-4) 和转化生长因子-β (TGF-β) 启动子的异常DNA甲基化

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Abstract

The pathogenesis of Behcet's disease (BD) remains poorly understood. The purpose of this study was to investigate whether an aberrant DNA methylation of transcriptional and inflammatory factors, including TBX21, GATA3, RORγt, FOXP3, IFN-γ, IL-4, IL-17A and TGF-β, in CD4(+)T confers risk to BD. We found that the promoter methylation level of GATA3, IL-4 and TGF-β was significantly up-regulated in active BD patients and negatively correlated with the corresponding mRNA expression. The mRNA expression of GATA3 and TGF-β was markedly down-regulated in active BD patients compared to healthy individuals. Treatment with corticosteroids and cyclosporine (CsA) resulted in a decrease of the methylation level of GATA3 and TGF-β in inactive BD patients. Our results suggest that an aberrant DNA methylation of GATA3 and TGF-β is associated with their mRNA expression and participates in the pathogenesis of BD.

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