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颞叶癫痫伴海马硬化 ILAE Ⅰ型患者的差异 DNA 甲基化图谱。

Differential DNA Methylation Profiles in Patients with Temporal Lobe Epilepsy and Hippocampal Sclerosis ILAE Type I.

机构信息

Department of Neurosurgery of the First Affiliate Hospital, Harbin Medical University, Harbin, China.

Department of Neurosurgery of Xing Tai People's Hospital, Xing Tai, China.

出版信息

J Mol Neurosci. 2021 Sep;71(9):1951-1966. doi: 10.1007/s12031-020-01780-9. Epub 2021 Jan 5.

Abstract

Hippocampal sclerosis (HS) is one of the most prevalent pathological types of temporal lobe epilepsy (TLE), and it significantly affects patient prognoses. The methylation of DNA plays an important role in the development of epilepsy. However, few studies have focused on HS subtypes to determine DNA methylation profiles in TLE. This study aimed to determine the pathogenesis of TLE from an epigenetic perspective in patients with TLE-HS type I (TLE-HSTI) and TLE without HS (TLE-nHS) using whole-genome bisulfite sequencing (WGBS). We defined 1171 hypermethylated and 2537 hypomethylated regions and found 632 differentially methylated genes (DMG) in the promoter region that were primarily involved in the regulation of various aspects of epilepsy development. Twelve DMG overlapped with differentially expressed genes (DEG) in the promoter region, and RT-qPCR findings revealed significant overexpression of the SBNO2, CBX3, RASAL3, and TMBIM4 genes in TLE-HSTI. We present the first systematic analysis of methylation profiles of TLE-HSTI and TLE-nHS from an epigenetic perspective using WGBS. Overall, our preliminary data highlight the underlying mechanism of TLE-HSTI, providing a new perspective for guiding treatment of TLE.

摘要

海马硬化症 (HS) 是颞叶癫痫 (TLE) 最常见的病理类型之一,它显著影响患者的预后。DNA 的甲基化在癫痫的发生发展中起着重要作用。然而,目前很少有研究关注 HS 亚型,以确定 TLE 中 DNA 甲基化图谱。本研究旨在通过全基因组亚硫酸氢盐测序 (WGBS) 从表观遗传学角度探讨 TLE-HS 型 I (TLE-HSTI) 和无 HS 的 TLE (TLE-nHS) 患者的发病机制。我们定义了 1171 个高甲基化和 2537 个低甲基化区域,并在启动子区域发现了 632 个差异甲基化基因 (DMG),这些基因主要参与了癫痫发生发展的各个方面的调控。12 个 DMG 与启动子区域的差异表达基因 (DEG) 重叠,RT-qPCR 结果显示 SBNO2、CBX3、RASAL3 和 TMBIM4 基因在 TLE-HSTI 中显著过表达。我们首次从表观遗传学角度对 TLE-HSTI 和 TLE-nHS 的甲基化谱进行了系统分析。总之,我们的初步数据强调了 TLE-HSTI 的潜在机制,为指导 TLE 的治疗提供了新的视角。

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