Abstract
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 language | English (US) |
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Article number | 111340 |
Journal | Nutrition |
Volume | 89 |
DOIs | |
State | Published - Sep 2021 |
Funding
This study was supported by R01 CA149633 (to Qi Dai and Chang Yu) and R01 CA202936 (to Qi Dai and Lifang Hou) from the National Cancer Institute, Department of Health and Human Services, as well as the Ingram Cancer Center Endowment Fund. Data collection, sample storage, and processing were partially conducted by the Survey and Biospecimen Shared Resource, which is supported in part by P30CA68485. Clinical visits to the Vanderbilt Clinical Research Center were supported in part by the Vanderbilt CTSA grant UL1 RR024975 from NCRR/NIH. The parent study data were stored in Research Electronic Data Capture (REDCap), and data analyses (VR12960) were supported in part by the Vanderbilt Institute for Clinical and Translational Research (UL1TR000445). All authors have no conflicts of interest. The Personalized Prevention of Colorectal Cancer Trial (PPCCT) was registered at clinicaltrials.gov as NCT01105169.
Keywords
- COVID-19
- Magnesium
- Methylation changes
- SARS-CoV-2
- TMPRSS2
ASJC Scopus subject areas
- Nutrition and Dietetics
- Endocrinology, Diabetes and Metabolism