Ischemic heart disease and stroke in relation to blood DNA methylation.
Ischemic heart disease and stroke in relation to blood DNA methylation.
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DOI：
10.1097/ede.0b013e3181f20457
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发表时间：
2010-11
期刊：
影响因子：
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通讯作者：
Schwartz J
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文献类型：
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作者：
Baccarelli A;Wright R;Bollati V;Litonjua A;Zanobetti A;Tarantini L;Sparrow D;Vokonas P;Schwartz J
表观遗传特征如DNA低甲基化与心血管风险相关的疾病有关。我们评估了在高度甲基化的重复序列中较低的血液DNA甲基化是否预测缺血性心脏病和中风的风险。我们通过PCR-焦磷酸测序对来自波士顿地区标准老化研究的712名老年人的LINE-1重复元件的血液DNA甲基化进行了定量。我们估计了缺血性心脏病和卒中的风险因素校正相对风险（RR）基线（242例流行病例）;以及发病率（44例新发病例;中位随访时间，63个月）;缺血性心脏病的后续死亡率（86例死亡;中位随访时间，75个月）。血液LINE-1低甲基化与基线缺血性心脏病（最低与最高甲基化四分位数的RR=2.1 [95%置信区间= 1.2至4.0]）和卒中（2.5 [0.9至7.5]）相关。在没有基线疾病的参与者中，甲基化低于中位数的个体也有更高的缺血性心脏病（4.0 [1.8至8.9]）或中风（5.7 [0.8至39.5]）风险。在整个队列中，甲基化低于中位数的人因缺血性心脏病（3.3 [1.3至8.4]）和中风（2.8 [0.6至14.3]）而死亡率较高。总死亡率也增加（2.0 [1.2至3.3]）。这些结果在使用LINE-1甲基化作为连续变量的其他回归模型中得到证实。患有流行性IHD和中风的受试者表现出较低的LINE-1甲基化。在纵向分析中，LINE-1甲基化水平较低的人发生缺血性心脏病和中风的风险较高，总死亡率也较高。
Epigenetic features such as DNA hypomethylation have been associated with conditions related to cardiovascular risk. We evaluated whether lower blood DNA methylation in heavily methylated repetitive sequences predicts the risk of ischemic heart disease and stroke. We quantified blood DNA methylation of LINE-1 repetitive elements through PCR-pyrosequencing in 712 elderly individuals from the Boston-area Normative Aging Study. We estimated risk-factor adjusted relative risks (RRs) for ischemic heart disease and stroke at baseline (242 prevalent cases); as well as in incidence (44 new cases; median follow-up, 63 months); and subsequent mortality from ischemic heart disease (86 deaths; median follow-up, 75 months). Blood LINE-1 hypomethylation was associated with baseline ischemic heart disease (RR=2.1 [95% confidence interval = 1.2 to 4.0] for lowest vs. highest methylation quartile) and for stroke (2.5 [0.9 to 7.5]). Among participants free of baseline disease, individuals with methylation below the median also had higher risk of developing ischemic heart disease (4.0 [1.8 to 8.9]) or stroke (5.7 [0.8 to 39.5]). In the entire cohort, persons with methylation below the median had higher mortality from ischemic heart disease (3.3 [1.3 to 8.4]) and stroke (2.8 [0.6 to 14.3]). Total mortality was also increased (2.0 [1.2 to 3.3]). These results were confirmed in additional regression models using LINE-1 methylation as a continuous variable. Subjects with prevalent IHD and stroke exhibited lower LINE-1 methylation. In longitudinal analyses, persons with lower LINE-1 methylation were at higher risk for incident ischemic heart disease and stroke, and for total mortality.