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

Abstract

\n Objectives\n The viral entry of SARS-CoV-2 requires host-expressed TMPRSS2 to facilitate the viral spike (S) protein priming. This study aims to test the hypothesis that Mg treatment leads to DNA methylation changes in TMPRSS2.\n \n \n Research Methods & Procedures\n This study is nested within the Personalized Prevention of Colorectal Cancer Trial (PPCCT), a double-blind 2\u202f×\u202f2 factorial randomized controlled trial, which enrolled 250 participants from Vanderbilt University Medical Center.\n \n Results\n We found that 12-week of personalized Mg treatment significantly increased 5-mC methylation at cg16371860 (TSS1500, promoter) by 7.2% compared to placebo arm (decreased by 0.1%) in those aged < 65 years old. The difference remained statistically significant after adjusting for age, sex and baseline methylation as well as FDR correction (FDR-adjusted P =0.014). Additionally, Mg treatment significantly reduced 5-hmC level at cg26337277 (close proximity to TSS200 and 5′UTR, promoter) by 2.3% compared to increases by 7.1% in the placebo arm after adjusting for covariates in those aged < 65 years old (P=0.003). The effect remained significant at FDR of 0.10 (adjusted P value=0.088).\n \n Conclusion\n Among individuals aged younger than 65 years with the Ca:Mg intake ratios equal to or over 2.6, reducing Ca:Mg ratios to around 2.3 increased 5-mC modifications (i.e. cg16371860) and reduced 5-hmC modifications (i.e. cg26337277) in the TMPRSS2 gene. These findings, if confirmed, provide another mechanism for the role of Mg intervention for the prevention of COVID-19 and treatment of early and mild disease by modifying the phenotype of the TMPRSS2 genotype.\n