Integrated DNA methylation and gene expression analysis in the pathogenesis of coronary artery disease
Integrated DNA methylation and gene expression analysis in the pathogenesis of coronary artery disease
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DOI：
10.18632/aging.101847
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发表时间：
2019-03-15
期刊：
影响因子：
5.2
通讯作者：
Wu, Jin-Zhen
中科院分区：
文献类型：
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作者：
Miao, Liu;Yin, Rui-Xing;Wu, Jin-Zhen
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及其可能的病理机制，我们进行了(1)对CAD样本和对照组的基因表达综合库中的外周血数据集进行了全基因组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) 11个感兴趣的差异甲基化位置和相应基因表达的验证试验；(4) DNA甲基化与mRNA表达数据的相关性分析。共有669个差异表达mrna与差异甲基化基因相匹配。通过疾病本体、京都基因与基因组百科通路、基因本体、蛋白-蛋白互作、网络构建和模块分析，共发现11个独特基因对应的11个差异甲基化位点（dmp）： BDNF-cg26949694、BTRC-cg24381155、CDH5 -cg02223351、CXCL12 - cg11267527、EGFR - cg27637738、il - cg13104385、ITGB1 - cg20545410、PDGFRB - cg25613180、PIK3R1- cg00559992、PLCB1 - cg27178677和PTPRC - cg09247619。在对11个目标dmp和相应基因表达进行验证测试后，我们发现CXCL12在CAD组中低甲基化程度较低，而ITGB1、PDGFRB和PIK3R1在CAD样品中的相对表达较低，并且CXCL12和ITGB1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CXCL12在CAD发病机制中的重要性。
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: BDNF-cg26949694, BTRC-cg24381155, CDH5 -cg02223351, CXCL12 - cg11267527, EGFR - cg27637738, IL-6 - cg13104385, ITGB1 - cg20545410, PDGFRB - cg25613180, PIK3R1- cg00559992, PLCB1 - cg27178677 and PTPRC - cg09247619. After validation tests of 11 DMPs of interest and the corresponding gene expression, we found that CXCL12 was less hypomethylated in the CAD group, whereas the relative expression of ITGB1, PDGFRB and PIK3R1 was lower in CAD samples, and CXCL12 and ITGB1 methylation was negatively correlated with their expression. This study identified the correlation between DNA methylation and gene expression and highlighted the importance of CXCL12 in CAD pathogenesis.