Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY (A.D.-R., R.A.G., K.S., M.G.-F., T.R.S., A.N.-A.).
Integrative Epidemiology Group, Department of Chronic Diseases Epidemiology, National Center for Epidemiology, Carlos III Health Institute, Madrid, Spain (A.D.-R., M.T.-P., M.G.-F.).
Circ Res. 2022 Jul 8;131(2):e51-e69. doi: 10.1161/CIRCRESAHA.122.320991. Epub 2022 Jun 6.
Epigenetic dysregulation has been proposed as a key mechanism for arsenic-related cardiovascular disease (CVD). We evaluated differentially methylated positions (DMPs) as potential mediators on the association between arsenic and CVD.
Blood DNA methylation was measured in 2321 participants (mean age 56.2, 58.6% women) of the Strong Heart Study, a prospective cohort of American Indians. Urinary arsenic species were measured using high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry. We identified DMPs that are potential mediators between arsenic and CVD. In a cross-species analysis, we compared those DMPs with differential liver DNA methylation following early-life arsenic exposure in the apoE knockout (apoE) mouse model of atherosclerosis.
A total of 20 and 13 DMPs were potential mediators for CVD incidence and mortality, respectively, several of them annotated to genes related to diabetes. Eleven of these DMPs were similarly associated with incident CVD in 3 diverse prospective cohorts (Framingham Heart Study, Women's Health Initiative, and Multi-Ethnic Study of Atherosclerosis). In the mouse model, differentially methylated regions in 20 of those genes and DMPs in 10 genes were associated with arsenic.
Differential DNA methylation might be part of the biological link between arsenic and CVD. The gene functions suggest that diabetes might represent a relevant mechanism for arsenic-related cardiovascular risk in populations with a high burden of diabetes.
表观遗传失调被认为是砷相关心血管疾病（CVD）的关键机制。我们评估了差异甲基化位置（DMP）作为砷与 CVD 之间关联的潜在介质。
在 2321 名美国印第安人的前瞻性队列研究——“强壮心脏研究”（Strong Heart Study）参与者的血液 DNA 甲基化水平进行了测量（平均年龄 56.2 岁，58.6%为女性）。采用高效液相色谱法-电感耦合等离子体质谱法测量尿砷形态。我们鉴定了砷与 CVD 之间潜在中介作用的 DMP。在种间分析中，我们比较了这些 DMP 与动脉粥样硬化 apoE 敲除（apoE）小鼠模型中早期生活砷暴露后的肝脏 DNA 甲基化差异。
共有 20 个和 13 个 DMP 分别是 CVD 发病和死亡的潜在介质，其中几个注释为与糖尿病相关的基因。在Framingham 心脏研究、妇女健康倡议和动脉粥样硬化多民族研究等 3 个不同的前瞻性队列中，其中 11 个 DMP 与 CVD 发病同样相关。在小鼠模型中，这些基因中有 20 个基因的差异甲基化区域和 10 个基因的 DMP 与砷有关。
DNA 甲基化差异可能是砷与 CVD 之间生物学联系的一部分。这些基因的功能表明，在糖尿病负担较重的人群中，糖尿病可能是砷相关心血管风险的一个相关机制。
