Kim Daniel, Kubzansky Laura D, Baccarelli Andrea, Sparrow David, Spiro Avron, Tarantini Letizia, Cantone Laura, Vokonas Pantel, Schwartz Joel
Department of Health Sciences, Northeastern University, Boston, Massachusetts, USA Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, Massachusetts, USA Department of Human and Social Sciences, EHESP French School of Public Health, Rennes, France.
Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, Massachusetts, USA.
BMJ Open. 2016 Jan 5;6(1):e009790. doi: 10.1136/bmjopen-2015-009790.
Although psychological factors have been associated with chronic diseases such as coronary heart disease (CHD), the underlying pathways for these associations have yet to be elucidated. DNA methylation has been posited as a mechanism linking psychological factors to CHD risk. In a cohort of community-dwelling elderly men, we explored the associations between positive and negative psychological factors with DNA methylation in promoter regions of multiple genes involved in immune/inflammatory processes related to atherosclerosis.
Prospective cohort study.
Greater Boston, Massachusetts area.
Samples of 538 to 669 men participating in the Normative Aging Study cohort with psychological measures and DNA methylation measures, collected on 1-4 visits between 1999 and 2006 (mean age=72.7 years at first visit).
We examined anxiety, depression, hostility and life satisfaction as predictors of leucocyte gene-specific DNA methylation. We estimated repeated measures linear mixed models, controlling for age, smoking, education, history of heart disease, stroke or diabetes, % lymphocytes, % monocytes and plasma folate.
Psychological distress measured by anxiety, depression and hostility was positively associated, and happiness and life satisfaction were inversely associated with average Intercellular Adhesion Molecule-1 (ICAM-1) and coagulation factor III (F3) promoter methylation levels. There was some evidence that hostility was positively associated with toll-like receptor 2 (TLR-2) promoter methylation, and that life satisfaction was inversely associated with TLR-2 and inducible nitric oxide synthase (iNOS) promoter methylation. We observed less consistent and significant associations between psychological factors and average methylation for promoters of the genes for glucocorticoid receptor (NR3C1), interferon-γ (IFN-γ) and interleukin 6 (IL-6).
These findings suggest that positive and negative psychological factors affect DNA methylation of selected genes involved in chronic immune/inflammatory processes and inflammation-related endothelial dysfunction. Such epigenetic changes may represent biological pathways that mediate the effects of psychological factors on CHD.
尽管心理因素已被证明与冠心病（CHD）等慢性疾病有关，但这些关联的潜在途径尚未阐明。DNA甲基化被认为是将心理因素与冠心病风险联系起来的一种机制。在一组社区居住的老年男性中，我们探讨了积极和消极心理因素与参与动脉粥样硬化相关免疫/炎症过程的多个基因启动子区域DNA甲基化之间的关联。
前瞻性队列研究。
马萨诸塞州大波士顿地区。
538至669名参与规范衰老研究队列的男性样本，在1999年至2006年期间进行了1 - 4次访视，收集了心理测量和DNA甲基化测量数据（首次访视时平均年龄 = 72.7岁）。
我们将焦虑、抑郁、敌意和生活满意度作为白细胞基因特异性DNA甲基化的预测指标。我们估计了重复测量线性混合模型，控制了年龄、吸烟、教育程度、心脏病、中风或糖尿病病史、淋巴细胞百分比、单核细胞百分比和血浆叶酸水平。
通过焦虑、抑郁和敌意测量的心理困扰与平均细胞间黏附分子 - 1（ICAM - 1）和凝血因子III（F3）启动子甲基化水平呈正相关，而幸福感和生活满意度与它们呈负相关。有证据表明，敌意与Toll样受体2（TLR - 2）启动子甲基化呈正相关，生活满意度与TLR - 2和诱导型一氧化氮合酶（iNOS）启动子甲基化呈负相关。我们观察到心理因素与糖皮质激素受体（NR3C1）、干扰素 - γ（IFN - γ）和白细胞介素6（IL - 6）基因启动子的平均甲基化之间的关联不太一致且不显著。
这些发现表明，积极和消极心理因素会影响参与慢性免疫/炎症过程和炎症相关内皮功能障碍的特定基因的DNA甲基化。这种表观遗传变化可能代表了介导心理因素对冠心病影响的生物学途径。
