哈萨克族原发性高血压病患者全血DNA甲基化位点筛查及异常甲基化谱的构建

发布时间：2018-07-31 12:54

【摘要】：目的应用基因芯片技术筛选哈萨克族原发性高血压病(EH)患者异常DNA甲基化位点,初步构建哈萨克族EH异常甲基化谱,为深入研究哈萨克族EH的发生机制提供理论依据。方法 2014年6月—2015年10月,在新疆乌鲁木齐县随机抽取哈萨克族牧民或半农牧民3 042例为调研对象,从其中的1 487例EH患者中随机选取3例作为EH组,并选取年龄匹配的3例健康者作为对照组。采用Illumina Human Methylation 450K Bead Chip芯片对两组受试者的全血进行全基因组DNA甲基化检测,筛选DNA异常甲基化位点,采用Gene Ontology(GO)富集分析和Pathway分析了解异常甲基化基因的功能。结果 EH组和对照组间存在427个差异甲基化位点,其中高甲基化位点148个,低甲基化位点279个;这些位点位于不同的染色体上,其中以1号和6号染色体最多,Y染色体未见差异甲基化位点;GO富集分析结果显示,差异甲基化基因主要参与糖蛋白生物合成与代谢、血管发育、脉管系统发展、胶原蛋白结合等生物学过程;Pathway分析结果显示,差异甲基化基因主要参与了硫酸软骨素生物合成、胰岛素信号通路、胞吞等。结论发生EH时DNA甲基化状态发生改变,多条差异甲基化基因与EH相关通路有关,但本研究仅是哈萨克族EH全基因组甲基化谱的开端,异常甲基化基因作为发生EH的候选分子标志物,若要获得更全面、更精确的结果,还需要进一步扩大样本量进行分析及验证。
[Abstract]:Objective to screen abnormal DNA methylation sites in Kazakh patients with essential hypertension (EH) by using gene chip technique, and to construct the abnormal methylation spectrum of EH in Kazakh population, and to provide a theoretical basis for further study on the pathogenesis of EH in Kazak nationality. Methods from June 2014 to October 2015, 3,042 Kazakh herdsmen or semi-farm herdsmen were randomly selected from Urumqi County, Xinjiang, and 3 of the 1,487 EH patients were randomly selected as EH group. Three age-matched healthy subjects were selected as control group. Illumina Human Methylation 450K Bead Chip chip was used to detect the whole genome DNA methylation in the whole blood of two groups of subjects. The abnormal methylation sites of DNA were screened, and the function of abnormal methylation gene was analyzed by Gene Ontology (GO) enrichment analysis and Pathway analysis. Results there were 427 differential methylation sites in EH group and control group, including 148 hypermethylation sites and 279 hypomethylation sites, which were located on different chromosomes. The results of enrichment analysis on chromosome 1 and chromosome 6 showed that differential methylation genes were mainly involved in glycoprotein biosynthesis and metabolism, vascular development and vascular system development. Biological processes such as collagen binding showed that differentially methylated genes were involved in chondroitin sulfate biosynthesis insulin signaling pathway and endocytosis. Conclusion the status of DNA methylation changes during EH, and many differentially methylated genes are related to EH related pathways, but this study is only the beginning of the whole genome methylation spectrum of EH in Kazak. The abnormal methylation gene is a candidate molecular marker for the occurrence of EH. In order to obtain more comprehensive and accurate results, it is necessary to further expand the sample size for analysis and verification.
【作者单位】：新疆医科大学护理学院;新疆医科大学医学实验动物中心;新疆医科大学第一附属医院;新疆乌鲁木齐市乌鲁木齐县甘沟乡卫生院;新疆乌鲁木齐市乌鲁木齐县小渠子乡卫生院;新疆乌鲁木齐市乌鲁木齐县水西沟镇中心卫生院;新疆乌鲁木齐市乌鲁木齐县板房沟乡中心卫生院;新疆医科大学公共卫生学院;
【基金】：新疆维吾尔自治区自然科学基金资助项目(2015211C020)
【分类号】：R544.11

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