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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。
Objective To screen abnormal DNA methylation sites in Kazakh patients with essential hypertension (EH) using gene chip technique and to construct an abnormal methylation profile of EH in Kazak, providing a theoretical basis for further study on the pathogenesis of EH in Kazakh. Methods From June 2014 to October 2015, 3 042 Kazakh herdsman or semi-herdsman and herder were randomly selected from Urumqi County of Xinjiang Uygur Autonomous Region for study. Among them, 1 487 EH patients were randomly selected as EH group and 3 Three age-matched healthy subjects were selected as control group. Whole-genome DNA methylation was detected in whole blood of two groups of subjects using Illumina Human Methylation 450K Bead Chip. The site of DNA abnormal methylation was screened, enrichment analysis by Gene Ontology (GO) and Pathway analysis were performed to find out abnormal A The function of the gene. Results There were 427 differentially methylated sites in the EH group and the control group, of which 148 were hypermethylated and 279 were hypomethylated. These loci were located on different chromosomes, of which 1 and 6 The most abundant chromosomes and the Y chromosome showed no differentially methylated sites. GO enrichment analysis showed that differential methylation genes were mainly involved in biological processes such as glycoprotein biosynthesis and metabolism, vascular development, vasculature development and collagen binding ; Pathway analysis showed that differential methylation genes are mainly involved in chondroitin sulfate biosynthesis, insulin signaling pathway, endocytosis and so on. Conclusions The DNA methylation status changes during EH occurrence. A number of differentially methylated genes are associated with EH-related pathways. However, this study is only the beginning of the methylation pattern of EH genome in Kazakh. The aberrant methylation of gene as EH Of candidate molecular markers, for more comprehensive and more accurate results, but also need to further expand the sample size for analysis and verification.