Epigenome-wide association of myocardial infarction with DNA methylation sites at loci related to cardiovascular disease.
Epigenome-wide association of myocardial infarction with DNA methylation sites at loci related to cardiovascular disease.
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DOI：
10.1186/s13148-017-0353-3
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发表时间：
2017
影响因子：
5.7
通讯作者：
Yokota M
中科院分区：
文献类型：
--
作者：
Nakatochi M;Ichihara S;Yamamoto K;Naruse K;Yokota S;Asano H;Matsubara T;Yokota M
心血管疾病（CVD）的发展，包括冠状动脉疾病、心律失常和缺血性中风，取决于环境和遗传因素。为了研究心肌梗死（MI）的表观遗传基础，我们对日本老年受试者进行了一项全表观基因组关联研究。共从住院患者和普通人群中招募了192名心肌梗死患者和192名对照患者。用Infinium HumanMethylation450 BeadChip分析获得全血DNA全基因组DNA甲基化（DNAm）谱。在对照组中评估了与心肌梗死显著相关的dna位点与附近的单核苷酸多态性（snp）的关系，这些snp先前被证明与CVD相关。三个DNAm位点（cg06642177、cg07786668、cg17218495）与MI在全基因组范围内显著相关（p分别为4.33 × 10−8、3.96 × 10−10和3.77 × 10−8）。其中两个位点（cg07786668、cg17218495）在调整MI经典危险因素后仍显示出这种相关性（p分别= 1.04 × 10−7和6.60 × 10−8）。DNAm位点cg07786668和cg17218495分别位于ZFHX3（锌指同源盒3）和SMARCA4 （SWI/ snf相关、基质相关、动作蛋白依赖的染色质调节因子a亚家族成员4）基因上。先前发现与CVD相关的ZFHX3或SMARCA4的snp在我们的对照受试者中与这些dna位点没有显著相关性。我们发现了两个DNAm位点——ZFHX3中的cg07786668和SMARCA4中的cg17218495，它们与心肌梗死有独立且显著的关联。我们的研究结果表明，心肌梗死的发生可能受到这些位点上DNAm变化的影响，其途径不同于这些基因中cvd相关snp的影响。Kita-Nagoya基因组流行病学（KING）研究是本研究中对照样本的来源，于2005年12月6日在ClinicalTrials.gov （NCT00262691）上注册。
Development of cardiovascular disease (CVD), including coronary artery disease, arrhythmia, and ischemic stroke, depends on environmental and genetic factors. To investigate the epigenetic basis of myocardial infarction (MI), we performed an epigenome-wide association study for this condition in elderly Japanese subjects. A total of 192 case subjects with MI and 192 control subjects were recruited from hospital attendees and the general population, respectively. Genome-wide DNA methylation (DNAm) profiles for DNA isolated from whole blood were obtained by analysis with an Infinium HumanMethylation450 BeadChip. The relation of DNAm sites found to be significantly associated with MI to nearby single nucleotide polymorphisms (SNPs) previously shown to be associated with CVD was assessed in the control group. Three DNAm sites (cg06642177, cg07786668, cg17218495) showed genome-wide significant associations with MI (p = 4.33 × 10−8, 3.96 × 10−10, and 3.77 × 10−8, respectively). Two of these sites (cg07786668, cg17218495) still showed such associations after adjustment for classical risk factors of MI (p = 1.04 × 10−7 and 6.60 × 10−8, respectively). The DNAm sites cg07786668 and cg17218495 are located in ZFHX3 (zinc finger homeobox 3) and SMARCA4 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4) genes, respectively. SNPs in ZFHX3 or SMARCA4 that were previously found to be associated with CVD were not significantly associated with these DNAm sites in our control subjects. We identified two DNAm sites—cg07786668 in ZFHX3 and cg17218495 in SMARCA4— that are independently and significantly associated with MI. Our results suggest that the development of MI might be influenced by changes in DNAm at these sites via a pathway that differs from that affected by CVD-associated SNPs in these genes. The Kita-Nagoya Genomic Epidemiology (KING) study, which was the source of control samples in the present study, was registered in ClinicalTrials.gov (NCT00262691) on 6 December 2005.