Zhang Jinming, Liu Zhonghua, Umukoro Peter E, Cavallari Jennifer M, Fang Shona C, Weisskopf Marc G, Lin Xihong, Mittleman Murray A, Christiani David C
a Department of Environmental Health , Harvard T. H. Chan School of Public Health , Boston , MA , USA.
b Department of Biostatistics , Harvard T. H. Chan School of Public Health , Boston , MA , USA.
Epigenetics. 2017 Feb;12(2):71-76. doi: 10.1080/15592294.2016.1270486. Epub 2017 Jan 11.
DNA methylation is one of the potential epigenetic mechanisms associated with various adverse cardiovascular effects; however, its association with cardiac autonomic dysfunction, in particular, is unknown. In the current study, we aimed to identify epigenetic variants associated with alterations in cardiac autonomic responses. Cardiac autonomic responses were measured with two novel markers: acceleration capacity (AC) and deceleration capacity (DC). We examined DNA methylation levels at more than 472,506 CpG probes through the Illumina Infinium HumanMethylation450 BeadChip assay. We conducted separate linear mixed models to examine associations of DNA methylation levels at each CpG with AC and DC. One CpG (cg26829071) located in the GPR133 gene was negatively associated with DC values after multiple testing corrections through false discovery rate. Our study suggests the potential functional importance of methylation in cardiac autonomic responses. Findings from the current study need to be replicated in future studies in a larger population.
DNA甲基化是与各种不良心血管效应相关的潜在表观遗传机制之一；然而，其与心脏自主神经功能障碍的关联，尤其是尚不清楚。在当前研究中，我们旨在识别与心脏自主神经反应改变相关的表观遗传变异。通过两种新的标志物测量心脏自主神经反应：加速能力（AC）和减速能力（DC）。我们通过Illumina Infinium HumanMethylation450 BeadChip检测法检测了超过472,506个CpG探针处的DNA甲基化水平。我们进行了单独的线性混合模型，以检查每个CpG处的DNA甲基化水平与AC和DC的关联。通过错误发现率进行多重检验校正后，位于GPR133基因中的一个CpG（cg26829071）与DC值呈负相关。我们的研究表明甲基化在心脏自主神经反应中具有潜在的功能重要性。当前研究的结果需要在未来更大规模人群的研究中进行重复验证。
