Genome wide DNA methylation profiling for epigenetic alteration in coronary artery disease patients
Genome wide DNA methylation profiling for epigenetic alteration in coronary artery disease patients
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DOI：
10.1016/j.gene.2014.02.034
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发表时间：
2014-05-10
期刊：
影响因子：
3.5
通讯作者：
Sengupta, Shantanu
中科院分区：
文献类型：
--
作者：
Sharma, Priyanka;Garg, Gaurav;Sengupta, Shantanu
背景：表观基因组的改变形成了基因型和环境之间的界面。表观遗传改变预计将对心血管疾病的发展做出重大贡献，其中环境相互作用在疾病进展中起关键作用。我们之前已经表明，整体DNA超甲基化本身与冠状动脉疾病（CAD）相关，并且高水平的同型半胱氨酸（一种巯基氨基酸，是心血管疾病的独立危险因素，也是大分子甲基化的关键调节剂）进一步加剧了这种高甲基化。我们已经确定了72个差异甲基化区域（DMR），在不同的同型半胱氨酸水平的背景下，CAD患者的高甲基化。在对一些选定的DMR进行深度亚硫酸氢盐测序后，我们发现CAD病例中甲基化显著较高。结论：本研究首次发现冠心病患者基因组中存在6个CpG位点的高甲基化，其中包括C1QL4基因的内含子区、CCDC47和TGFBR 3基因的上游区。需要在不同人群中进行进一步验证，以便将这一信息用于疾病风险评估和管理。(C)2014爱思唯尔有限公司版权所有。
Background: The alteration in the epigenome forms an interface between the genotype and the environment. Epigenetic alteration is expected to make a significant contribution to the development of cardiovascular disease where environmental interactions play a key role in disease progression. We had previously shown that global DNA hypermethylation per se is associated with coronary artery disease (CAD) and is further accentuated by high levels of homocysteine, a thiol amino acid which is an independent risk factor for cardiovascular disease and is also a key modulator of macromolecular methylation.Results: We have identified 72 differentially methylated regions (DMRs) that were hypermethylated in CAD patients in the background of varying homocysteine levels. Following deep bisulfite sequencing of a few of the selected DMRs, we found significantly higher methylation in CAD cases. We get six CpG sites in three DMRs that included the intronic region of C1QL4 gene and upstream region of CCDC47 and TGFBR3 genes.Conclusion: To the best of our knowledge, this is the first study to identify hypermethylated regions across the genome in patients with coronary artery disease. Further validation in different populations is necessary for this information to be used for disease risk assessment and management. (C) 2014 Elsevier B.V. All rights reserved.