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

Autor: Fan L; Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Zhu X; Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Zheng Y; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA., Zhang W; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA., Seidner DL; Center for Human Nutrition, Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease and Surgical Institute, Cleveland Clinic, Cleveland, Ohio, USA., Ness R; Department of Medicine, Division of Gastroenterology, Vanderbilt School of Medicine, Nashville, Tennessee, USA., Murff HJ; Division of Geriatric Medicine, General Internal Medicine and Public Health, Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Yu C; Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA., Huang X; Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Shrubsole MJ; Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Hou L; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA., Dai Q; Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA. Electronic address: qi.dai@vanderbilt.edu.
Jazyk: angličtina
Zdroj: Nutrition (Burbank, Los Angeles County, Calif.) [Nutrition] 2021 Sep; Vol. 89, pp. 111340. Date of Electronic Publication: 2021 May 07.
DOI: 10.1016/j.nut.2021.111340
Abstrakt: 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.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: