Research Laboratories, P. D. Hinduja Hospital & Medical Research Centre, Mumbai, India.
Department of Cardiology, P. D. Hinduja Hospital & Medical Research Centre, Mumbai, India.
Mol Biol Rep. 2019 Feb;46(1):541-550. doi: 10.1007/s11033-018-4507-y. Epub 2018 Nov 23.
Epidemiological studies have revealed that coronary artery disease (CAD) is highly heritable. However, genetic studies have not been able to fully elucidate its etiology. Accumulating evidences suggest that epigenetic alterations like DNA methylation may provide an alternative and additional explanation of its pathophysiology. DNA methylation regulates hypomethylation and hypermethylation of various genes which are involved in the development of CAD. Our aim was to identify differentially methylated regions (DMRs) in genome of CAD patients by using the microarray chip having a coverage of > 4,50,000 CpG sites (Illumina's Infinium HumanMethylation450 BeadChip). In this pilot study, an epigenome-wide analysis of DNA methylation from whole blood was performed in six angiographically positive male cases, who were age and gender matched with six angiographically negative controls. All subjects were non-smokers, non-diabetic, non-alcoholic, with no previous history of cardiac ailment. Illumina's GenomeStudio (v 2011.1) software was used to identify DMRs and pathway analysis, gene ontology was carried out using DAVID (Database for Annotation, Visualisation and Integrated Discovery). 429 DMRs were found to be significant of which 222 were hypomethylated and 207 were hypermethylated. Antigen processing and presentation was identified to be the most significant biological function with a statistical significance of p = 4.35 × 10. HLA-DRB1, HLA-DQA1, HLA-DQB1 along with non-classical HLA molecules HLA-G, HLA-C are responsible for triggering the inflammatory pathway which have been identified in our study. To the best of our knowledge, this is the first study to identify a panel of DMRs using a high coverage microarray chip in India.
流行病学研究表明，冠状动脉疾病（CAD）具有高度遗传性。然而，遗传研究还不能完全阐明其病因。越来越多的证据表明，表观遗传改变，如 DNA 甲基化，可能为其病理生理学提供另一种解释。DNA 甲基化调节各种基因的低甲基化和高甲基化，这些基因参与 CAD 的发生。我们的目的是通过使用覆盖 >450,000 个 CpG 位点的微阵列芯片（Illumina 的 Infinium HumanMethylation450 BeadChip）来鉴定 CAD 患者基因组中的差异甲基化区域（DMRs）。在这项初步研究中，对来自全血的 DNA 甲基化进行了全基因组范围内的表观基因组分析，涉及 6 名血管造影阳性的男性病例，他们与 6 名血管造影阴性的对照者在年龄和性别上相匹配。所有受试者均不吸烟、无糖尿病、无酗酒史，也没有心脏疾病的既往病史。使用 Illumina 的 GenomeStudio（v 2011.1）软件来识别 DMRs 和途径分析，使用 DAVID（Database for Annotation, Visualisation and Integrated Discovery）进行基因本体论分析。发现 429 个 DMRs 具有统计学意义，其中 222 个呈低甲基化，207 个呈高甲基化。抗原加工和呈递被确定为最显著的生物学功能，其统计学意义为 p=4.35×10-10。HLA-DRB1、HLA-DQA1、HLA-DQB1 以及非经典 HLA 分子 HLA-G、HLA-C 负责触发炎症途径，这在我们的研究中已经得到证实。据我们所知，这是在印度首次使用高覆盖率微阵列芯片鉴定 DMRs 面板的研究。
