Department of Neurology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People's Republic of China.
Haihe Laboratory of Cell Ecosystem, Tianjin, People's Republic of China.
Clin Interv Aging. 2023 Aug 1;18:1221-1232. doi: 10.2147/CIA.S421830. eCollection 2023.
BACKGROUND/OBJECTIVE: Dyskinesia caused by transient ischemic attack (TIA) and mild ischemic stroke (MIS) is mild and short-lived; however, cognitive impairment (CI) can occur in the acute phase and be easily overlooked. DNA methylation is an epigenetic phenomenon that can affect gene expression through gene silencing. Blood levels of matrix metalloproteinase (MMP) 9 are elevated in ischemic stroke patients and is associated with the destruction of the blood-brain barrier and the occurrence of CI. No studies have investigated the relationship between gene methylation and TIA/MIS with early cognitive impairment (ECI). As such, the purpose of the present study was to investigate the correlation between gene methylation and TIA/MIS with ECI.
Data from 112 subjects were collected, including 84 with TIA/MIS (National Institutes of Health Stroke Scale <5 points) and 28 non-stroke control subjects. Patients were evaluated within 7 days of TIA/MIS onset according to four single-domain cognitive scales. Whole blood DNA methylation was detected using MethylTarget sequencing technology. Comparison of gene methylation levels among subgroups was performed using statistical methods.
The site S33-79 in the TIA/MIS group was hypomethylated compared with the control group, and sites S33-25 and S33-30 in TIA/MIS with ECI was hypomethylated compared with TIA/MIS without ECI. Compared with the small artery occlusion group, gene, S33-25, 30, 39, 53, 58, 73, 79, 113 and 131 sites in the large artery atherosclerosis group were hypomethylated.
gene hypomethylation sites were associated with TIA/MIS and TIA/MIS with ECI, and there was a strong correlation between gene hypomethylation and atherosclerotic TIA/MIS. gene methylation can reflect the severity of TIA/MIS. gene hypomethylation sites may be used as potential biomarkers and therapeutic targets for TIA/MIS and TIA/MIS with ECI.
背景/目的：短暂性脑缺血发作（TIA）和轻度缺血性卒中（MIS）引起的运动障碍较轻且短暂；然而，认知障碍（CI）可在急性期发生且容易被忽视。DNA 甲基化是一种表观遗传现象，可通过基因沉默影响基因表达。缺血性卒中患者血液中基质金属蛋白酶（MMP）9 水平升高，与血脑屏障破坏和 CI 发生有关。目前尚无研究探讨基因甲基化与 TIA/MIS 伴早期认知障碍（ECI）的关系。因此，本研究旨在探讨基因甲基化与 TIA/MIS 伴 ECI 的相关性。
收集了 112 例受试者的数据，包括 84 例 TIA/MIS（美国国立卫生研究院卒中量表<5 分）和 28 例非卒中对照组。患者在 TIA/MIS 发病后 7 天内根据四项单域认知量表进行评估。采用 MethylTarget 测序技术检测全血 DNA 甲基化水平。采用统计学方法比较亚组间基因甲基化水平。
TIA/MIS 组 S33-79 位点较对照组低甲基化，TIA/MIS 伴 ECI 组 S33-25 和 S33-30 位点较 TIA/MIS 无 ECI 组低甲基化。与小动脉闭塞组相比，大动脉粥样硬化组基因 S33-25、30、39、53、58、73、79、113 和 131 位点低甲基化。
基因低甲基化位点与 TIA/MIS 和 TIA/MIS 伴 ECI 相关，基因低甲基化与动脉粥样硬化性 TIA/MIS 密切相关。基因甲基化可反映 TIA/MIS 的严重程度。基因低甲基化位点可能作为 TIA/MIS 和 TIA/MIS 伴 ECI 的潜在生物标志物和治疗靶点。
