Vitamin D receptor gene methylation in patients with hand, foot, and mouth disease caused by enterovirus 71

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 56 , 0.73; AUC 68 , 0.699; AUC 42 , 0.694; AUC 66 , 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.