Cardiovascular Epidemiology and Genetics Research Group, REGICOR Study Group, IMIM (Hospital Del Mar Medical Research Institute), Barcelona, Catalonia, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
Cardiovascular Epidemiology and Genetics Research Group, REGICOR Study Group, IMIM (Hospital Del Mar Medical Research Institute), Barcelona, Catalonia, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain; CIBER Cardiovascular Diseases (CIBERCV), Barcelona, Catalonia, Spain.
Atherosclerosis. 2017 Aug;263:325-333. doi: 10.1016/j.atherosclerosis.2017.05.022. Epub 2017 May 18.
The aim of this study was to perform a systematic review of the association between DNA methylation and coronary heart disease (CHD) or related atherosclerotic traits.
A systematic review was designed. The condition of interest was DNA methylation, and the outcome was CHD or other atherosclerosis-related traits. Three DNA methylation approaches were considered: global methylation, candidate-gene, and epigenome-wide association studies (EWAS). A functional analysis was undertaken using the Ingenuity Pathway Analysis software.
In total, 51 articles were included in the analysis: 12 global methylation, 34 candidate-gene and 11 EWAS, with six studies using more than one approach. The results of the global methylation studies were inconsistent. The candidate-gene results were consistent for some genes, suggesting that hypermethylation in ESRα, ABCG1 and FOXP3 and hypomethylation in IL-6 were associated with CHD. The EWAS identified 84 genes showing differential methylation associated with CHD in more than one study. The probability of these findings was <1.37·10. One third of these genes have been related to obesity in genome-wide association studies. The functional analysis identified several diseases and functions related to these set of genes: inflammatory, metabolic and cardiovascular disease.
Global DNA methylation seems to be not associated with CHD. The evidence from candidate-gene studies was limited. The EWAS identified a set of 84 genes highlighting the relevance of obesity, inflammation, lipid and carbohydrate metabolism in CHD. This set of genes could be prioritized in future studies assessing the role of DNA methylation in CHD.
本研究旨在系统综述 DNA 甲基化与冠心病（CHD）或相关动脉粥样硬化特征之间的关联。
设计了一项系统综述。感兴趣的条件是 DNA 甲基化，结果是 CHD 或其他与动脉粥样硬化相关的特征。考虑了三种 DNA 甲基化方法：全基因组甲基化、候选基因和表观基因组全基因组关联研究（EWAS）。使用Ingenuity Pathway Analysis 软件进行了功能分析。
共有 51 篇文章纳入分析：12 篇全基因组甲基化、34 篇候选基因和 11 篇 EWAS，其中 6 项研究使用了不止一种方法。全基因组甲基化研究的结果不一致。一些基因的候选基因结果一致，提示 ESRα、ABCG1 和 FOXP3 高甲基化以及 IL-6 低甲基化与 CHD 相关。EWAS 确定了 84 个基因，这些基因在超过一项研究中显示与 CHD 相关的差异甲基化。这些发现的概率<1.37·10。这些基因中有三分之一在全基因组关联研究中与肥胖有关。功能分析确定了与这组基因相关的几种疾病和功能：炎症、代谢和心血管疾病。
全基因组 DNA 甲基化似乎与 CHD 无关。候选基因研究的证据有限。EWAS 确定了一组 84 个基因，突出了肥胖、炎症、脂质和碳水化合物代谢在 CHD 中的相关性。这组基因可能在未来评估 DNA 甲基化在 CHD 中的作用的研究中被优先考虑。
