Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital.
Jean Mayer-United States Department of Agriculture Human Nutrition Research Center on Aging, Boston, Massachusetts, USA.
Curr Opin Clin Nutr Metab Care. 2020 Jul;23(4):236-240. doi: 10.1097/MCO.0000000000000659.
DNA methylation is an epigenetic mark that reflects both genetic and environmental influences over the life course and has the potential to be a robust biomarker for cardiovascular disease (CVD) risk. However, standard association studies linking DNA methylation and CVD are susceptible to reverse causation and may not directly translate into useful biomarkers of future disease. Studies of incident CVD represent a crucial tool for improving this evidence base.
Recent investigations have started to provide links between DNA methylation and incident CVD. Epigenome-wide association studies have suggested individual genetic loci in which differential methylation exists prior to disease onset, while multivariate predictive modeling approaches have made progress towards realizing the potential for DNA methylation as a predictive biomarker of CVD risk. Meanwhile, complementary analysis strategies such as Mendelian randomization have provided clues as to the causality of these epigenomic associations.
Taken together, this wave of studies provides the basis for a better understanding of CVD pathophysiology and the development of more confident biomarkers of CVD risk.
综述目的：DNA 甲基化是一种表观遗传标记，反映了生命过程中的遗传和环境影响，有可能成为心血管疾病（CVD）风险的强大生物标志物。然而，将 DNA 甲基化与 CVD 联系起来的标准关联研究容易受到反向因果关系的影响，并且可能无法直接转化为未来疾病的有用生物标志物。CVD 发病研究代表了改善这一证据基础的重要工具。
最新发现：最近的研究开始提供 DNA 甲基化与 CVD 发病之间的联系。全基因组关联研究表明，在疾病发生之前，存在个体遗传基因座中存在差异甲基化，而多元预测建模方法在实现 DNA 甲基化为 CVD 风险预测生物标志物的潜力方面取得了进展。与此同时，孟德尔随机化等互补分析策略为这些表观基因组关联的因果关系提供了线索。
总结：综上所述，这一波研究为更好地理解 CVD 病理生理学和开发更有信心的 CVD 风险生物标志物奠定了基础。
