Magnesium treatment on methylation changes of transmembrane serine protease 2 (TMPRSS2).
Magnesium treatment on methylation changes of transmembrane serine protease 2 (TMPRSS2).
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DOI：
10.1016/j.nut.2021.111340
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Dai Q
中科院分区：
文献类型：
--
作者：
Fan L;Zhu X;Zheng Y;Zhang W;Seidner DL;Ness R;Murff HJ;Yu C;Huang X;Shrubsole MJ;Hou L;Dai Q
SARS-CoV-2的病毒进入需要宿主表达的TMPRSS2来促进病毒尖峰蛋白的启动。本研究旨在验证镁处理导致TMPRSS2中DNA甲基化改变的假设。这项研究嵌套在个性化预防结直肠癌试验中，这是一项双盲2×2因素随机对照试验，从范德比尔特大学医学中心招募了250名参与者。我们发现，在这些年龄65岁的患者中，12周的个体化镁治疗显著增加了cg16371860(TSS1500，启动子)的5-甲基胞嘧啶甲基化，与安慰剂组(减少0.1%)相比，增加了7.2%。在调整了年龄、性别和基线甲基化以及修正了错误发现率后，差异仍然具有统计学意义(调整后P=0.014)。此外，镁治疗显著降低了cg26337277(接近TSS200和5‘非翻译区，启动子)的5-羟甲基胞嘧啶水平2.3%，而安慰剂组在调整这些年龄和65岁的相关变量后增加了7.1%(P=0.003)。这种影响仍然显著，错误发现率为0.10%(调整后P=0.088)。在65岁的钙镁摄入量比率等于或超过2.6的人中，将这一比率降低到2.3左右，增加了TMPRSS2基因的5-甲基胞嘧啶修饰(即cg16371860)，减少了5-羟甲基胞嘧啶修饰(即cg26337277)。这些发现如果得到证实，将为镁干预通过改变TMPRSS2基因的表型在预防新冠肺炎和治疗早期和轻度疾病中的作用提供另一种机制。
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. 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. 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). 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.
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