Department of Sleep Medicine, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453002, China.
The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China.
Sleep Breath. 2024 Dec;28(6):2397-2407. doi: 10.1007/s11325-024-03145-7. Epub 2024 Aug 26.
As the most common sleep disorder, chronic insomnia disorder (CID) has become a global health burden to the public. However, it remains unclear about the pathogenesis of this disease. Epigenetic changes may provide important insights into the gene-environment interaction in CID. Therefore, this study was conducted to investigate the DNA methylation pattern in CID and reveal the epigenetic mechanism of this disease.
In this study, whole blood DNA was extracted from 8 CID patients (the CID group) and 8 healthy controls (the control group), respectively. Besides, genome-wide DNA methylation was detected by Illumina Human Methylation 850 K Beadchip. Moreover, the sleep quality and insomnia severity were evaluated by the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI), respectively.
A total of 369 differentially methylated positions (DMPs) and 23 differentially methylated regions (DMRs) were identified between the CID and control groups. LHX6 was identified as the most important differentially methylated gene (DMG). The Gene Ontology (GO) analysis results corroborated that DMPs were significantly enriched in 105 GO terms, including cell signaling, homogenous cell adhesion of plasma membrane adhesion molecules, nervous system development, cell adhesion, and calcium ion binding. In addition, it was demonstrated that DMPs were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including the hippo signaling pathway, Ras signaling pathway, and vitamin B6 metabolism. The DMR-related GO analysis results revealed the positive regulation of protein kinase activities.
DNA methylation plays a critical role in the development of CID, and LHX6 is validated to be an important DMG.
作为最常见的睡眠障碍，慢性失眠障碍（CID）已成为全球公共卫生的负担。然而，其发病机制尚不清楚。表观遗传变化可能为 CID 中的基因-环境相互作用提供重要的见解。因此，本研究旨在探讨 CID 中的 DNA 甲基化模式，揭示该疾病的表观遗传机制。
本研究分别从 8 名 CID 患者（CID 组）和 8 名健康对照者（对照组）中提取全血 DNA。采用 Illumina Human Methylation 850 K Beadchip 检测全基因组 DNA 甲基化。此外，分别采用匹兹堡睡眠质量指数（PSQI）和失眠严重程度指数（ISI）评估睡眠质量和失眠严重程度。
CID 组和对照组之间共鉴定出 369 个差异甲基化位置（DMP）和 23 个差异甲基化区域（DMR）。LHX6 被鉴定为最重要的差异甲基化基因（DMG）。GO 分析结果表明，DMP 显著富集于 105 个 GO 术语，包括细胞信号转导、质膜粘附分子的同质细胞黏附、神经系统发育、细胞黏附和钙离子结合。此外，还表明 DMP 显著富集于京都基因与基因组百科全书（KEGG）通路，包括 hippo 信号通路、Ras 信号通路和维生素 B6 代谢。DMR 相关 GO 分析结果揭示了蛋白激酶活性的正调控。
DNA 甲基化在 CID 的发生发展中起着关键作用，LHX6 被验证为一个重要的 DMG。
