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

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Abstract

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.

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Availability of data and material

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank the doctors of the Department of Infectious Diseases of Xi’an Children’s Hospital and Xi’an Jiaotong University Second Affiliated Hospital for their help with sample collection. The authors also thank the Shanghai Genesky Bio-Tech Center for Human Genetics Research for technical assistance with genotyping.

Funding

This work was supported by the National Natural Science Foundation of China (Grant number 81701632) and Shaanxi Natural Science Foundation of China (Grant number S2019-JC-QN-0055).

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Authors and Affiliations

  1. Department of Infectious Diseases, Xi’an Jiaotong University Second Affiliated Hospital, No. 157 Xiwu Road, Xi’an, 710004, China

    Ya-Ping Li, Hui-Ling Deng, Wen-Jun Wang, Mu-Qi Wang, Mei Li & Shuang-Suo Dang

  2. Department of Infectious Diseases, Xi’an Children’s Hospital, Xi’an, 710003, China

    Hui-Ling Deng, Yu-Feng Zhang & Jun Wang

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  1. Ya-Ping Li
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Correspondence to Shuang-Suo Dang.

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The author(s) declare that they have no competing interests.

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This study was approved by the Medical Ethics Committee of Xi’an Jiaotong University Second Affiliated Hospital and Xi’an Children’s Hospital, Xi’an, China.

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Handling Editor: Akbar Dastjerdi.

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Li, YP., Deng, HL., Wang, WJ. et al. Vitamin D receptor gene methylation in patients with hand, foot, and mouth disease caused by enterovirus 71. Arch Virol 165, 1979–1985 (2020). https://doi.org/10.1007/s00705-020-04701-8

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  • DOI: https://doi.org/10.1007/s00705-020-04701-8

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