To evaluate the epigenetic regulation of the VDR gene in enterovirus 71 (EV71)-associated severe hand, foot, and mouth disease (HFMD), a total of 116 patients with EV71-HFMD, including 58 with mild EV71-HFMD and 58 with severe EV71-HFMD, as well as 60 healthy controls, were enrolled in this study. Quantitative real-time PCR was used to measure the relative levels of VDR mRNA expression, and the methylation status of the VDR promoter was assessed using a MethylTarget™ assay. The DNA methylation levels of the VDR promoter in children with EV71-associated severe HFMD were lower than those in the healthy controls and in children with mild HFMD (P < 0.05). Hypomethylation at CpG site 133 and hypermethylation at the CpG 42 sites and 68 downregulated VDR expression. Moreover, the methylation level of VDR could be used for differential diagnosis of mild and severe EV71-associated HFMD (AUC56, 0.73; AUC68, 0.699; AUC42, 0.694; AUC66, 0.693). VDR expression and promoter methylation were associated with the progression of EV71 infection. Determining the VDR promoter status might help clinicians initiate the appropriate strategy for treatment of EV71-associated HFMD.

中文翻译：

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肠道病毒引起的手足口病患者的维生素D受体基因甲基化71。

为了评估肠道病毒71（EV71）相关的严重手足口病（HFMD）中VDR基因的表观遗传调控，共有116例EV71-HFMD患者，包括58例轻度EV71-HFMD和58例重度EV71-HFMD这项研究纳入了EV71-HFMD以及60个健康对照。实时定量PCR用于测量VDR mRNA表达的相对水平，并使用MethylTarget™分析评估VDR启动子的甲基化状态。EV71相关严重HFMD儿童的VDR启动子的DNA甲基化水平低于健康对照组和轻度HFMD儿童的VDR启动子的DNA甲基化水平（P <0.05）。CpG位点133处的甲基化不足，CpG 42位点和68位的甲基化不足，VDR表达下调。此外，VDR的甲基化水平可用于轻度和重度EV71相关手足口病的鉴别诊断（AUC56，0.73； AUC68，0.699； AUC42，0.694； AUC66，0.693）。VDR表达和启动子甲基化与EV71感染的进展有关。确定VDR启动子状态可能有助于临床医生启动适当的策略来治疗EV71相关的手足口病。