急性ST段抬高型心肌梗死甲基化谱的研究

Study of DNA methylated Gene in acute ST segment elevation myocardial infarction

目的 应用甲基化芯片对急性ST段抬高型心肌梗死甲基化谱的研究,初步探讨急性ST段抬高型心肌梗死中甲基化谱的调控网络.方法 选择2009年12月至2011年6月间本院在急诊科首诊并确诊为STEMI的男性患者10人,及同期本院健康体检年龄匹配的男性10人作为对照组,采用甲基化DNA免疫沉淀,分别与两张NimbleGen CpG启动子芯片进行杂交,对杂交信号标准化和比对分析.利用SigMap和DAVID生物信息学工具对筛选基因进行染色体定位、功能分类和通路分析.结果 STEMI组与对照组对比的DMRs的数量为1 634个,其中分布于HCP的量为1480个（90.57％）、ICP的量为131个（8.02％）和LCP的量为23个（1.41％）;GO分析和Pathway分析显示STEMI组发生甲基化变化有显著性差异基因分布的信号通路有甘油磷酯代谢、半胱氨酸和甲硫氨酸代谢、扩张型心肌病、致心律失常右室心肌病、肌动蛋白细胞骨架调节、钙离子信号通路等,而与脂质代谢相关的信号通路其甲基化变化无显著差异.结论 运用甲基化芯片和生物信息学工具可快速、高通量地分析甲基化芯片数据,并实现对STEMI甲基化基因初步功能分类.

Objective To investigate the regulatory networks of DNA methylation profiles in STEMI by methylation microarrays.Methods A total often male patients with STEMI and ten male healthy controls were recruited.Methyl-DNA immunoprecipitation and Nimblegen HG18 Meth 385K promoter plus CpG island microarrays were used to identify differentially methylated regions.And several bioinformatics analysis tools which included chromosomal assignment, gene ontology analysis and pathway analysis with SignalMap and The Database for Annotation, Visualization and Integrated Discovery were used to high-throughput analysis.Results Compared with healthy controls, DMRs of STEMI is 1 634, There are 1 480 （90.57%）, 131 （8.02%） and23 （1.41%） methylated sites were separately located on High CpG-containing promoter, Intermediate CpG-containing promoter and Low CpG-containing promoter;Gene Ontology and Pathway analysis expressed DNA methylated genes of signaling pathway in MI identified glycerophespholipid metabolism, cysteine and methionine metabolism, Dilated cardiomyopathy, Arrhythmogenic right ventricular cardiomyopathy, regulation of actin cyteskeleton, calcium signaling pathway.However, the signal pathway about lipid metabolism is shown no significant difference.Conclusions Bioinformatics tools could provide the quick and high-throughput analysis of data from methylation microarray and enable the function classification of differentially expressed genes of STEMI.