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首页> 外文期刊>Gene: An International Journal Focusing on Gene Cloning and Gene Structure and Function >Genome wide DNA methylation profiling for epigenetic alteration in coronary artery disease patients
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Genome wide DNA methylation profiling for epigenetic alteration in coronary artery disease patients

机译:全基因组DNA甲基化分析用于冠心病患者的表观遗传改变

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摘要

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.
机译:背景:表观基因组的改变形成了基因型和环境之间的界面。表观遗传改变有望为心血管疾病的发展做出重要贡献,其中环境相互作用在疾病进展中起关键作用。先前我们已经表明,全球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进一步加重了该水平,高硫半胱氨酸是心血管疾病的独立危险因素,也是大分子的关键调节剂甲基化。结果:我们确定了72个差异甲基化区域(DMR),这些区域在高半胱氨酸水平变化的背景下在CAD患者中甲基化程度较高。在对一些选定的D​​MR进行亚硫酸氢盐深度测序后,我们发现CAD病例的甲基化程度明显更高。我们在三个DMR中获得了六个CpG位点,其中包括C1QL4基因的内含子区域以及CCDC47和TGFBR3基因的上游区域。结论:据我们所知,这是第一项在冠心病患者中鉴定基因组中高甲基化区域的研究。为了使该信息用于疾病风险评估和管理,有必要在不同人群中进行进一步验证。

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