Epigenetic Biomarkers of Lead Exposure and Cardiovascular Disease: Prospective Evidence in the Strong Heart Study.
Epigenetic Biomarkers of Lead Exposure and Cardiovascular Disease: Prospective Evidence in the Strong Heart Study.
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DOI：
10.1161/jaha.122.026934
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发表时间：
2022-12-06
影响因子：
5.4
通讯作者：
Kupsco A
中科院分区：
文献类型：
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作者：
Lieberman-Cribbin W;Domingo-Relloso A;Navas-Acien A;Cole S;Haack K;Umans J;Tellez-Plaza M;Colicino E;Baccarelli AA;Gao X;Kupsco A
铅是一种心脏毒性金属，对健康有多种不良影响。在缺乏骨铅暴露数据的情况下，表观遗传生物标志物可以作为累积铅暴露和身体负荷的指标。在此，我们利用铅暴露的新型表观遗传生物标志物来研究其与心血管疾病（CVD）发病率和死亡率的相关性。使用Illumina MethylationEPIC BeadChip在基线（1989-1991）时测量了2231名强心研究（SHS）参与者的血液DNA甲基化。使用先前确定的胞嘧啶-鸟嘌呤二核苷酸（CpG）位点估计血液、髌骨和胫骨中铅水平的表观遗传生物标志物。CVD发病率和死亡率数据截至2017年。胫骨、髌骨和血液中铅表观遗传生物标志物的中位浓度分别为13.8 μg/g、21.3 μg/g和2.9 μg/dL。在调整后的模型中，胫骨电极导线、髌骨电极导线和血铅的表观遗传生物标志物每增加一倍的CVD死亡率风险比（HR）（95% CI）分别为1.42（1.07-1.87）、1.22（0.93-1.60）和1.57（1.16-2.11）。发生CVD的相应HR分别为0.99（0.83-1.19）、1.07（0.89-1.29）和1.06（0.87-1.30）。胫骨导联表观遗传生物标志物与CVD死亡率之间的相关性按性别进行了修改（相互作用P值：0.014），男性风险（HR，1.42 [95% CI，1.17-1.72]）高于女性（HR，1.04 [95% CI，0.89-1.22]）。胫骨和血液表观遗传生物标志物与CVD死亡风险增加相关，可能反映了累积和近期铅暴露对心血管的影响。这些发现支持铅暴露的表观遗传生物标志物可能捕获与铅暴露相关的一些疾病风险。
Lead is a cardiotoxic metal with a variety of adverse health effects. In the absence of data on bone lead exposure, epigenetic biomarkers can serve as indicators of cumulative lead exposure and body burden. Herein, we leveraged novel epigenetic biomarkers of lead exposure to investigate their association with cardiovascular disease (CVD) incidence and mortality. Blood DNA methylation was measured using the Illumina MethylationEPIC BeadChip among 2231 participants of the Strong Heart Study (SHS) at baseline (1989–1991). Epigenetic biomarkers of lead levels in blood, patella, and tibia were estimated using previously identified cytosine‐guanine dinucleotide (CpG) sites. CVD incidence and mortality data were available through 2017. Median concentrations of lead epigenetic biomarkers were 13.8 μg/g, 21.3 μg/g, and 2.9 μg/dL in tibia, patella, and blood, respectively. In adjusted models, the hazard ratio (HR) (95% CI) of CVD mortality per doubling increase in lead epigenetic biomarkers were 1.42 (1.07–1.87) for tibia lead, 1.22 (0.93–1.60) for patella lead, and 1.57 (1.16–2.11) for blood lead. The corresponding HRs for incident CVD were 0.99 (0.83–1.19), 1.07 (0.89–1.29), and 1.06 (0.87–1.30). The association between the tibia lead epigenetic biomarker and CVD mortality was modified by sex (interaction P value: 0.014), with men at increased risk (HR, 1.42 [95% CI, 1.17–1.72]) compared with women (HR, 1.04 [95% CI, 0.89–1.22]). Tibia and blood epigenetic biomarkers were associated with increased risk of CVD mortality, potentially reflecting the cardiovascular impact of cumulative and recent lead exposures. These findings support that epigenetic biomarkers of lead exposure may capture some of the disease risk associated with lead exposure.