Research Paper Volume 11, Issue 18 pp 7663—7677

Association between promoter DNA methylation and gene expression in the pathogenesis of ischemic stroke

Guo-Xiong Deng 1, , Ning Xu 2, , Qi Huang 2, , Jin-Yue Tan 1, , Zhao Zhang 2, , Xian-Feng Li 2, , Jin-Ru Wei 1, ,

  • 1 Department of Cardiology, The First People’s Hospital of Nanning City, Nanning, Guangxi 530021, China
  • 2 Department of Neurology, The First People’s Hospital of Nanning City, Nanning, Guangxi 530021, China

received: July 28, 2019 ; accepted: September 7, 2019 ; published: September 17, 2019 ;

https://doi.org/10.18632/aging.102278
How to Cite

Copyright © 2019 Deng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

To assess DNA methylation sites as well as gene expression related to ischemic stroke (IS) and comprehensively reveal their correlation and possible pathological mechanisms, we implemented (1) genome-wide DNA methylation profiling from the GEO repository related to IS with and without symptoms; (2) identification of differentially methylation positions (DMPs) and genes (DMGs), functional enrichment analysis along with DMG regulatory network construction; (3) validation tests of 2 differential methylation positions of interest as well as analogous gene expression in other datasets and in IS patients and controls; and (4) correlation analysis of DNA methylation and mRNA expression data. In total, 870 DMPs were physically located within 693 DMGs. After disease ontology (DO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, gene ontology (GO), protein-protein interaction (PPI) network construction as well as module analysis, HLA-DRB1 and HLA-DQB1 were identified. Their expression was validated in 4 other datasets but was significant in only 1, and the expression was lower in the IS group (P < 0.05). After validation in IS patients and controls, we found that these two genes showed more hypermethylation and lower expression levels in the IS group (P < 0.001). The methylation of genes was negatively associated with their expression (P < 0.05). The current study recognized a connection among DNA methylation and gene expression and emphasized the prominence of HLA-DRB1 and HLA-DQB1 in IS pathogenesis.

Abbreviations

TIA: including transient ischemic attack; IS: ischemic stroke; GEO: Gene Expression Omnibus; GEO2R: Gene Expression Omnibus 2 R; DEG: differentially expressed genes; DMP: differential methylation position; DMG: differentially methylation genes; MRA: Multi-array Average; DO: disease ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; GO: gene ontology; FDR: false discovery rate; PPI: Protein-protein interaction; MCODE: Molecular Complex Detection; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; Apo: apolipoprotein; PCR: Polymerase Chain Reaction; IBD: Inflammatory bowel disease; cAMP: Cyclic Adenosine monophosphate; PI3K-Akt: phosphatidylinositol 3′-kinase-Akt; CHR: chromosome; MAPINFO: position in Build 37; IBD: Inflammatory bowel disease; CE: cardiac aortic embolism; SAD: arteriolar disease; LAA: arteriosclerosis; MTRNR2L8: recombinant Human Humanin-like protein 8; ABCA1: ATP binding cassette subfamily A member 1; HLA-A: human leukocyte antigen A; HLA-B: human leukocyte antigen B; HLA-C: human leukocyte antigen C; HLA-DR: human leukocyte antigen DR; HLA-DP: human leukocyte antigen DP; HLA-DQ: human leukocyte antigen DQ; HLA-DRB1: human leukocyte antigen DR beta 1; HLA-DQB1: human leukocyte antigen DQ beta 1.