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

IF 5.7 2区医学 Q1 Medicine Clinical Epigenetics Pub Date : 2023-06-27 DOI:10.1186/s13148-023-01520-x

Hao Peng, Helena Palma-Gudiel, Carolina Soriano-Tarraga, Jordi Jimenez-Conde, Mingzhi Zhang, Yonghong Zhang, Jinying Zhao

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Abstract

Background: DNA 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.

Results: Genome-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.

Conclusions: Altered DNA methylation of the TRIM6, TLN2, and FLRT2 genes may play a functional role in ischemic stroke in Chinese populations.

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全表观基因组关联研究发现与缺血性卒中相关的新基因。

背景:DNA甲基化先前与缺血性卒中有关，但具体的基因及其在缺血性卒中中的功能作用仍有待确定。在这里，我们的目的是确定在中国人群缺血性卒中中发挥功能作用的差异甲基化基因。结果:在包括80名中国成年人(40例与40例对照)的发现样本中，使用Illumina甲基化EPIC阵列对全基因组DNA甲基化进行评估，发现缺血性卒中患者的特征是6个CpG位点(分别位于TRIM6、FLRT2、SOX1、SOX17、AGBL4和FAM84A)的DNA甲基化增加，另一个位点(位于TLN2)的DNA甲基化减少。靶向亚硫酸酯测序在独立的中国人群中证实了6个差异甲基化探针(853例，对照918例)，一个探针(位于TRIM6)在外部欧洲队列中进一步验证(207例，对照83例)。对工程人脐静脉内皮细胞DNA甲基化的实验操作表明，鉴定的位于TRIM6、TLN2和FLRT2基因的差异甲基化探针可能在内皮细胞粘附和动脉粥样硬化中发挥作用。结论:TRIM6、TLN2和FLRT2基因甲基化改变可能在中国人群缺血性卒中中发挥功能作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Epigenetics Biochemistry, Genetics and Molecular Biology-Developmental Biology

CiteScore

8.90

自引率

5.30%

发文量

150

审稿时长

12 weeks

期刊介绍： Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.