Magnesium treatment on methylation changes of transmembrane serine protease 2 (TMPRSS2)

Lei Fan, Xiangzhu Zhu, Yinan Zheng, Wei Zhang, Douglas L. Seidner, Reid Ness, Harvey J. Murff, Chang Yu, Xiang Huang, Martha J. Shrubsole, Lifang Hou, Qi Dai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Objectives: The viral entry of SARS-CoV-2 requires host-expressed TMPRSS2 to facilitate the viral spike protein priming. This study aims to test the hypothesis that magnesium (Mg) treatment leads to DNA methylation changes in TMPRSS2. Methods: This study is nested within the Personalized Prevention of Colorectal Cancer Trial, a double-blind 2 × 2 factorial randomized controlled trial, which enrolled 250 participants from Vanderbilt University Medical Center. Results: We found that 12 wk of personalized Mg treatment significantly increased 5-methylcytosine methylation at cg16371860 (TSS1500, promoter) by 7.2% compared to the placebo arm (decreased by 0.1%) in those ages < 65 y. The difference remained statistically significant after adjusting for age, sex, and baseline methylation as well as correction for false discovery rate (adjusted P = 0.014). Additionally, Mg treatment significantly reduced 5-hydroxymethylcytosine levels at cg26337277 (close proximity to TSS200 and the 5′ untranslated region, promoter) by 2.3% compared to an increase of 7.1% in the placebo arm after adjusting for covariates in those ages < 65 y (P = 0.003). The effect remained significant at a false discovery rate of 0.10 (adjusted P = 0.088). Conclusions: Among individuals ages < 65 y with calcium-to-magnesium intake ratios equal to or over 2.6, reducing the ratio to around 2.3 increased 5-methylcytosine modifications (i.e., cg16371860) and reduced 5-hydroxymethylcytosine modifications (i.e., cg26337277) in the TMPRSS2 gene. These findings, if confirmed, provide another mechanism for the role of Mg intervention in the prevention of COVID-19 and treatment of early and mild disease by modifying the phenotype of the TMPRSS2 genotype.

Original languageEnglish (US)
Article number111340
StatePublished - Sep 2021


  • COVID-19
  • Magnesium
  • Methylation changes
  • SARS-CoV-2

ASJC Scopus subject areas

  • Nutrition and Dietetics
  • Endocrinology, Diabetes and Metabolism


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