Department of Infectious Diseases, Xi'an Jiaotong University Second Affiliated Hospital, No. 157 Xiwu Road, Xi'an, 710004, China.
Department of Infectious Diseases, Xi'an Children's Hospital, Xi'an, 710003, China.
Arch Virol. 2020 Sep;165(9):1979-1985. doi: 10.1007/s00705-020-04701-8. Epub 2020 Jun 18.
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 (AUC, 0.73; AUC, 0.699; AUC, 0.694; AUC, 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.
为了评估肠道病毒 71（EV71）相关重症手足口病（HFMD）中 VDR 基因的表观遗传调控，本研究共纳入了 116 例 EV71-HFMD 患儿，其中 58 例为轻症 EV71-HFMD 患儿，58 例为重症 EV71-HFMD 患儿，以及 60 例健康对照者。采用实时定量 PCR 检测 VDR mRNA 表达的相对水平，并采用 MethylTargetTM 检测 VDR 启动子的甲基化状态。EV71 相关重症 HFMD 患儿 VDR 启动子的 DNA 甲基化水平低于健康对照组和轻症 HFMD 患儿（P<0.05）。CpG 位点 133 的低甲基化和 CpG 42 位点和 68 位点的高甲基化下调了 VDR 的表达。此外，VDR 的甲基化水平可用于区分轻症和重症 EV71 相关 HFMD（AUC，0.73；AUC，0.699；AUC，0.694；AUC，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为 EV71 相关 HFMD 制定适当的治疗策略。
