全基因组关联研究鉴定出与缺血性脑卒中相关的新基因。
Epigenome-wide association study identifies novel genes associated with ischemic stroke.
机构信息
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, Suzhou, 215123, China.
Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida, 2004 Mowry Road, Gainesville, FL, 32610, USA.
出版信息
Clin Epigenetics. 2023 Jun 27;15(1):106. doi: 10.1186/s13148-023-01520-x.
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.
背景
DNA 甲基化先前与缺血性脑卒中相关，但具体基因及其在缺血性脑卒中的功能作用仍有待确定。本研究旨在鉴定在中国人中与缺血性脑卒中具有功能相关性的差异甲基化基因。
结果
通过在包括 80 名中国成年人（40 例病例与 40 例对照）的发现样本中使用 Illumina Methylation EPIC 阵列进行全基因组 DNA 甲基化评估，发现缺血性脑卒中患者的六个 CpG 位点（分别位于 TRIM6、FLRT2、SOX1、SOX17、AGBL4 和 FAM84A 上）的 DNA 甲基化水平升高，一个额外的位点（TLN2 上）的 DNA 甲基化水平降低。在一个独立的中国人群（853 例病例与 918 例对照）中，通过靶向亚硫酸氢盐测序验证了这些差异甲基化探针中的六个，一个探针（位于 TRIM6 上）在一个外部欧洲队列（207 例病例与 83 例对照）中进一步得到验证。在工程化的人脐静脉内皮细胞中对 DNA 甲基化的实验操作表明，鉴定出的位于 TRIM6、TLN2 和 FLRT2 基因的差异甲基化探针可能在血管内皮细胞黏附和动脉粥样硬化中发挥作用。
结论
TRIM6、TLN2 和 FLRT2 基因的 DNA 甲基化改变可能在中国人缺血性脑卒中发病中发挥功能作用。
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