慢性心力衰竭患者全基因组的甲基化改变  

Altered whole genomic methylation in chronic heart failure patients

作　　者：王建龙[1] 李海涛[1] 苏丕雄[2] 顾松[2] 刘岩[2] 张希涛[2] 颜钧[2] 安向光[2] 高杰[2] 辛悦[2] 蔡军[2] 

机构地区：[1]北京市普仁医院心内科,北京100062 [2]首都医科大学附属北京朝阳医院心脏中心,北京100020

出　　处：《首都医科大学学报》2012年第4期427-431,共5页Journal of Capital Medical University

基　　金：国家自然科学基金面上项目(81070193)~~

摘　　要：目的研究全基因组甲基化对心力衰竭患者心肌基因表达的影响。方法取心脏移植中供体左心室心肌标本8例作为正常对照组,行心脏移植的心力衰竭患者自身左心室心肌标本14例作为实验组,提取基因组基因通过甲基化DNA免疫共沉淀结合甲基化芯片技术(methylated DNA immunoprecipitation-chip,MeDIP-chip)及基因表达谱芯片进行高通量的快速筛选。然后,得到MeDIP-chip初筛后的2个甲基化异常基因abca4和cd200进行亚硫酸氢钠测序PCR。结果疾病组abca4基因启动子区甲基化率为85.5%,正常组基因启动子区甲基化率为91.2%;疾病组基因启动子区甲基化率比正常组基因启动子区甲基化率低5.7%,心衰组cd200基因启动子区甲基化率为50.5%,正常组基因启动子区甲基化率为57.1%。结论 abca4和cd200启动子区甲基化改变会影响自身的基因表达量。心衰时DNA启动子区甲基化会发生改变,并且DNA启动子区的甲基化会伴随着基因表达量的改变。Objective To explore the relationship between the change of whole genome methylation and heart failure. Methods Methylated DNA Immunoprecipitation-chip （MeDIP-chip） and microarray hybridization, mRNA amplification and microarray, and the bisulfite sequencing（ BS）-PCR-sequencing strategy were used in this study. Differential methylation genes and differential expression genes from mRNA amplication and microarray analysis were compared. Then 13 differential methylation genes were selected for further analysis with BS-PCR. Results abca4 gene promoter methylation in heart failure group and healthy group was 85.5% and 91.2% , respectively. While 5.7% difference in methylation between two groups correlated with 2.05 fold increase in mRNA expression in heart failure group, cd200 gene promoter methylation in heart failure group and healthy group was 50.5% and 57.1% respectively. And 6.6% difference in methylation between two groups corresponded to 2.18 fold increase in mRNA expression in heart failure group. Conclusion abca4 and cd200 DNA methylation may significantly influence the expression of these genes. And it is suggested that the alteration in DNA methylation may lead to the initiation and development of heart failure.

关 键 词：DNA甲基化 abca4 CD200 表观遗传 心力衰竭 

分 类 号：Q75[生物学—分子生物学]