Repetitive element DNA methylation and circulating endothelial and inflammation markers in the VA normative aging study.
Repetitive element DNA methylation and circulating endothelial and inflammation markers in the VA normative aging study.
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DOI：
10.4161/epi.5.3.11377
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发表时间：
2010-04
期刊：
影响因子：
3.7
通讯作者：
Schwartz J
中科院分区：
文献类型：
--
作者：
Baccarelli A;Tarantini L;Wright RO;Bollati V;Litonjua AA;Zanobetti A;Sparrow D;Vokonas PS;Schwartz J
较低的血液DNA甲基化与动脉粥样硬化和高心血管风险相关。DNA低甲基化与心血管疾病风险增加之间的联系机制在很大程度上仍然未知。在社区居住的老年人群体中，我们评估了LINE-1重复元件中的DNA甲基化，高度甲基化的序列分散在整个人类基因组中，是否与循环血管细胞粘附分子-1（VCAM-1），细胞间粘附分子-1（ICAM-1）和C-反应蛋白（CRP）相关。我们通过亚硫酸氢盐PCR-焦磷酸测序对来自波士顿地区标准老化研究（平均年龄=74.8岁）男性参与者的742份血液DNA样本进行LINE-1甲基化测定。平均血清VCAM-1与LINE-1低甲基化相关逐渐增加（最高与最低甲基化五分位数中从975.2至1063.4 ng/ml; p趋势=0.004）。VCAM-1和LINE-1低甲基化之间的关联在没有缺血性心脏病或中风的个体中是显著的（n=480; p=0.001），但在患有流行性疾病的个体中不是（n=262; p=0.57）。血清ICAM-1和CRP与LINE-1甲基化无关（p趋势=>0.25）。所有结果均经多变量分析证实，调整了年龄、BMI、吸烟、包年数和缺血性心脏病/卒中。LINE-1元件低甲基化与较高的血清VCAM-1相关。我们的数据为可能伴随心血管疾病发展的表观遗传事件提供了新的见解。
Lower blood DNA methylation has been associated with atherosclerosis and high cardiovascular risk. Mechanisms linking DNA hypomethylation to increased cardiovascular risk are still largely unknown. In a population of community-dwelling elderly individuals, we evaluated whether DNA methylation in LINE-1 repetitive element, heavily methylated sequences dispersed throughout the human genome, was associated with circulating Vascular Cell Adhesion Molecule-1 (VCAM-1), Inter-Cellular Adhesion Molecule-1 (ICAM-1), and C-reactive protein (CRP). We measured LINE-1 methylation by bisulfite PCR-Pyrosequencing on 742 blood DNA samples from male participants in the Boston area Normative Aging Study (mean age=74.8 years). Mean serum VCAM-1 increased progressively in association with LINE-1 hypomethylation (from 975.2 to 1063.4 ng/ml in the highest vs. lowest methylation quintiles; p-trend=0.004). The association between VCAM-1 and LINE-1 hypomethylation was significant in individuals without ischemic heart disease or stroke (n=480; p=0.001), but not in those with prevalent disease (n=262; p=0.57). Serum ICAM-1 and CRP were not associated with LINE-1 methylation (p-trend=>0.25). All results were confirmed by multivariable analyses adjusting for age, BMI, smoking, pack-years, and ischemic heart disease/stroke. LINE-1 element hypomethylation is associated with higher serum VCAM-1. Our data provide new insights into epigenetic events that may accompany the development of cardiovascular disease.