Epigenome-wide association study identifies novel genes associated with ischemic stroke

Clinical Epigenetics

Research

Helena Palma-Gudiel¹  Jinying Zhao¹  Hao Peng²  Yonghong Zhang²  Mingzhi Zhang²  Jordi Jimenez-Conde³  Carolina Soriano-Tarraga⁴ 

[1] Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida, 2004 Mowry Road, 32610, Gainesville, FL, USA;Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, 199 Renai Road, 215123, Suzhou, China;Neurovascular Research Group, Department of Neurology of Hospital del Mar-IMIM (Institut Hospital del Mar d’Investigacions Mèdiques), Universitat Autònoma de Barcelona/DCEXS, Universitat Pompeu Fabra, Barcelona, Spain;Neurovascular Research Group, Department of Neurology of Hospital del Mar-IMIM (Institut Hospital del Mar d’Investigacions Mèdiques), Universitat Autònoma de Barcelona/DCEXS, Universitat Pompeu Fabra, Barcelona, Spain;Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA;Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA;NeuroGenomics and Informatics, Department of Psychiatry, Washington University in St. Louis, St. Louis, USA;

关键词: DNA methylation;    Ischemic stroke;    EWAS;    CRISPR/dCas9-Dnmt3a;    Chinese population;   

DOI  :  10.1186/s13148-023-01520-x

 received in 2023-04-24, accepted in 2023-06-13,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundDNA methylation has previously been associated with ischemic stroke, but the specific genes and their functional roles in ischemic stroke remain to be determined. Here we aimed to identify differentially methylated genes that play a functional role in ischemic stroke in a Chinese population.ResultsGenome-wide DNA methylation assessed with the Illumina Methylation EPIC Array in a discovery sample including 80 Chinese adults (40 cases vs. 40 controls) found that patients with ischemic stroke were characterized by increased DNA methylation at six CpG loci (individually located at TRIM6, FLRT2, SOX1, SOX17, AGBL4, and FAM84A, respectively) and decreased DNA methylation at one additional locus (located at TLN2). Targeted bisulfite sequencing confirmed six of these differentially methylated probes in an independent Chinese population (853 cases vs. 918 controls), and one probe (located at TRIM6) was further verified in an external European cohort (207 cases vs. 83 controls). Experimental manipulation of DNA methylation in engineered human umbilical vein endothelial cells indicated that the identified differentially methylated probes located at TRIM6, TLN2, and FLRT2 genes may play a role in endothelial cell adhesion and atherosclerosis.ConclusionsAltered DNA methylation of the TRIM6, TLN2, and FLRT2 genes may play a functional role in ischemic stroke in Chinese populations.

【 授权许可】

CC BY   
© The Author(s) 2023

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