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冠状动脉疾病发病机制中DNA甲基化与基因表达的综合分析

Integrated DNA methylation and gene expression analysis in the pathogenesis of coronary artery disease.

作者信息

Miao Liu, Yin Rui-Xing, Zhang Qing-Hui, Hu Xi-Jiang, Huang Feng, Chen Wu-Xian, Cao Xiao-Li, Wu Jin-Zhen

机构信息

Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, China.

Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Disease Control and Prevention, Nanning 530021, Guangxi, China.

出版信息

Aging (Albany NY). 2019 Mar 7;11(5):1486-1500. doi: 10.18632/aging.101847.

Abstract

To evaluate DNA methylation sites and gene expression associated with coronary artery disease (CAD) and the possible pathological mechanism involved, we performed (1) genome-wide DNA methylation and mRNA expression profiling in peripheral blood datasets from the Gene Expression Omnibus repository of CAD samples and controls; (2) functional enrichment analysis and differential methylation gene regulatory network construction; (3) validation tests of 11 differential methylation positions of interest and the corresponding gene expression; and (4) correlation analysis for DNA methylation and mRNA expression data. A total of 669 differentially expressed mRNAs were matched to differentially methylated genes. After disease ontology, Kyoto Encyclopedia of Genes and Genomes pathway, gene ontology, protein-protein interaction and network construction and module analyses, 11 differentially methylated positions (DMPs) corresponding to 11 unique genes were observed: - cg26949694, - cg24381155, - cg02223351, - cg11267527, - cg27637738, - cg13104385, - cg20545410, - cg25613180, - cg00559992, - cg27178677 and - cg09247619. After validation tests of 11 DMPs of interest and the corresponding gene expression, we found that was less hypomethylated in the CAD group, whereas the relative expression of , and was lower in CAD samples, and and methylation was negatively correlated with their expression. This study identified the correlation between DNA methylation and gene expression and highlighted the importance of in CAD pathogenesis.

摘要

为了评估与冠状动脉疾病(CAD)相关的DNA甲基化位点和基因表达以及其中可能涉及的病理机制,我们进行了以下操作:(1)在来自CAD样本和对照的基因表达综合数据库的外周血数据集中进行全基因组DNA甲基化和mRNA表达谱分析;(2)功能富集分析和差异甲基化基因调控网络构建;(3)对11个感兴趣的差异甲基化位点及其相应基因表达进行验证测试;(4)对DNA甲基化和mRNA表达数据进行相关性分析。总共669个差异表达的mRNA与差异甲基化基因相匹配。经过疾病本体论、京都基因与基因组百科全书通路、基因本体论、蛋白质-蛋白质相互作用以及网络构建和模块分析后,观察到与11个独特基因相对应的11个差异甲基化位点(DMPs):- cg26949694、- cg24381155、- cg02223351、- cg11267527、- cg27637738、- cg13104385、- cg20545410、- cg25613180、- cg00559992、- cg27178677和- cg09247619。在对11个感兴趣的DMPs及其相应基因表达进行验证测试后,我们发现CAD组中[此处原文缺失具体基因名称]的低甲基化程度较低,而CAD样本中[此处原文缺失具体基因名称]、[此处原文缺失具体基因名称]和[此处原文缺失具体基因名称]的相对表达较低,并且[此处原文缺失具体基因名称]和[此处原文缺失具体基因名称]的甲基化与其表达呈负相关。本研究确定了DNA甲基化与基因表达之间的相关性,并强调了[此处原文缺失具体基因名称]在CAD发病机制中的重要性。

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