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  

Blood Screening for DNA Methylation Sites and Construction of Aberrant Methylation Profile in Kazak Essential Hypertensive Patients

作　　者：由淑萍[1] 从美丽[2] 倪国华[3] 詹怀峰 王红军 金晶 马登娥 叶力夏提 赵志强[1] 蒋红[1] 刘涛[8] 

机构地区：[1]新疆医科大学护理学院,新疆乌鲁木齐市830000 [2]新疆医科大学医学实验动物中心,新疆乌鲁木齐市830054 [3]新疆医科大学第一附属医院,新疆乌鲁木齐市830054 [4]新疆乌鲁木齐市乌鲁木齐县甘沟乡卫生院,830000 [5]新疆乌鲁木齐市乌鲁木齐县小渠子乡卫生院,830000 [6]新疆乌鲁木齐市乌鲁木齐县水西沟镇中心卫生院,830000 [7]新疆乌鲁木齐市乌鲁木齐县板房沟乡中心卫生院,830000 [8]新疆医科大学公共卫生学院,新疆乌鲁木齐市830054

出　　处：《中国全科医学》2017年第6期678-683,共6页Chinese General Practice

基　　金：新疆维吾尔自治区自然科学基金资助项目(2015211C020)

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。Objective To screen aberrant DNA methylation sites of Kazak essential hypertension（EH）by using gene chip technique,and construct Kazak EH aberrant methylation profiles preliminarily,so as to provide a theoretical basis for intensive study of the mechanism of Kazak EH. Methods From June 2014 to October 2015,using random sampling method, 3 042 Kazak herdsmen or semi - nomads were selected as the participants of this study from Urumqi County. Of them,1 487 had EH. And from the 1 487 EH patients,3 were randomly selected as the EH group,and other 3 age - matched healthy volunteers as the control group. Using Illumina Human Methylation 450K BeadChip,we measured the whole blood of all subjects for detecting DNA methylation and screening the aberrant methylation sites of DNA. We analyzed the function of abnormal methylation genes by using Gene Ontology（GO）enrichment analysis and Pathway analysis. Results There were 427 significantly differential methylated sites in EH and normal groups,where in 148 high methylation sites,279 low methylation sites;these sites were located on different chromosomes;among them,chromosome 1 and chromosome 6 were the most,no differential methylated site was found in Y chromosome. GO enrichment analysis showed that aberrant methylation genes mainly involved in the processes of glycoprotein biosynthesis and metabolism,vascular development,vasculature development,collagen binding and so on. Pathway analysis demonstrated that aberrant methylation genes mainly played a part in chondroitin sulfate biosynthesis,insulin signaling pathway,endocytosis and so forth. Conclusion The occurrence of EH involves in the changes in DNA methylation status. A number of differential methylated genes are related with EH associated signaling pathway. This study is only the beginning of construction of Kazak EH genome methylation profile,and the obtained aberrant methylation gene can be considered as a candidate early risk molecular marker of EH. However,more comprehensive and accurate study results need the a

关 键 词：高血压 哈萨克族 DNA甲基化 基因芯片 

分 类 号：R544.1[医药卫生—心血管疾病]