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作 者:赖伟华[1] 潘伟祥[1] 冯颖青[2] 余细勇[3] 陈纪言[2] 钟诗龙[2,3]
机构地区:[1]广东省人民医院/广东省医学科学院药学部,广州510080 [2]广东省心血管病研究所心内科,广州510080 [3]广东省人民医院/广东省医学科学院医学研究部,广州510080
出 处:《中国药房》2015年第35期4938-4941,共4页China Pharmacy
基 金:广东省科技计划项目(No.2012A03040062;No.2013B021800157);广东省医学科研基金立项课题(No.A2013039)
摘 要:目的:探究冠心病(CHD)患者与健康志愿者全基因组甲基化的差异,从表观遗传学角度初步探讨DNA甲基化与CHD的相关性。方法:采用病例对照研究法,将受试者分为CHD组(CHD患者50例)和健康对照组(Health组,健康志愿者50例),采用甲基化DNA免疫共沉淀测序(Me DIP-Seq)法对两组受试者DNA进行测序,分析比较其全基因组甲基化的差异。结果:CHD组甲基化峰(Peak)的数量高于Health组,差异有统计学意义(P<0.05)。Peak主要分布在5’UTR、Intron基因功能元件上。CHD组APQ1、SHB等基因启动子区域内的reads数低于Health组,其甲基化水平降低;而GRK5基因及染色体chr X上多个基因启动子区域内的reads数则高于Health组,其甲基化水平增高,差异均有统计学意义(P<0.01)。结论:CHD患者全基因组甲基化水平高于健康志愿者,相关基因启动子甲基化水平的变化可能与CHD的发生有关。OBJECTIVE:To explore the genome-wide methylation differences between coronary heart disease(CHD) patients and healthy volunteers,and to investigate the relationsip of DNA methylation with CHD from epigenetics. METHODS:In case-control study,subjects were divided into CHD group(50 cases)and health control group(50 cases). DNA of 2 groups were sequenced with methylated DNA immunoprecipitation sequencing technology. The genome-wide methylation differences were analyzed and compared between 2 groups. RESULTS:The number of methylation peak in CHD group was higher than health group,with statistical signficance(P〈0.05). The methylation peak mainly distributed in 5'UTR,Intron functional elements. The number of reads in AQP1,SHB and other gene promoters in CHD group were lower than health group,and its methylation level decreased. The number of reads in GRK5 and serveal gene promoters on chr X in CHD group were higher than helath group,and its methylation level increased,with statistical significance(P〈0.01). CONCLUSIONS:The genome-wide methylation level of CHD patients are higher than those of healthy volunteers. The occurence of CHD is possibly associated with the change of methylation level of related gene promoters.
关 键 词:冠心病 DNA甲基化 甲基化DNA免疫共沉淀测序
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