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重度阻塞性睡眠呼吸暂停患者中阿尔茨海默病相关基因表达的改变。

Alterations in Alzheimer's Disease-Associated Gene Expression in Severe Obstructive Sleep Apnea Patients.

作者信息

Li Hsueh-Yu, Tsai Ming-Shao, Huang Chung-Guei, Wang Robert Y L, Chuang Li-Pang, Chen Ning-Hung, Liu Chi-Hung, Hsu Cheng-Ming, Cheng Wen-Nuan, Lee Li-Ang

机构信息

Department of Otolaryngology-Head and Neck Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.

Faculty of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.

出版信息

J Clin Med. 2019 Sep 1;8(9):1361. doi: 10.3390/jcm8091361.

Abstract

BACKGROUND

Obstructive sleep apnea (OSA) increases the risk of Alzheimer's disease (AD), and inflammation may be involved in the early pathogenesis of AD in patients with OSA. However, the potential pathways between OSA and AD have yet to be established. In this study, we aimed to investigate differential expressions of AD-associated genes in OSA patients without evident AD or dementia.

METHODS

This prospective case-control study included five patients with severe OSA and five age and sex-matched patients with non-severe OSA without evident dementia who underwent uvulopalatopharyngoplasty between 1 January 2013 and 31 December 2015. The expressions of genes associated with AD were analyzed using whole-exome sequencing. Unsupervised two-dimensional hierarchical clustering was performed on these genes. Pearson's correlation was used as the distance metric to simultaneously cluster subjects and genes.

RESULTS

The expressions of , , , , and in the patients with severe OSA were significantly different from those in the patients with non-severe OSA and contributed to changes in the immune response, cytokine-cytokine receptor interactions, and nucleotide-binding oligomerization domain-like receptor signaling pathways.

CONCLUSIONS

Inflammation may contribute to the onset of AD and physicians need to be aware of the potential occurrence of AD in patients with severe OSA.

摘要

背景

阻塞性睡眠呼吸暂停(OSA)会增加患阿尔茨海默病(AD)的风险,炎症可能参与了OSA患者AD的早期发病机制。然而,OSA与AD之间的潜在途径尚未明确。在本研究中,我们旨在调查无明显AD或痴呆的OSA患者中AD相关基因的差异表达。

方法

这项前瞻性病例对照研究纳入了2013年1月1日至2015年12月31日期间接受悬雍垂腭咽成形术的5例重度OSA患者和5例年龄及性别匹配的无明显痴呆的非重度OSA患者。使用全外显子测序分析与AD相关的基因表达。对这些基因进行无监督二维层次聚类。使用Pearson相关性作为距离度量来同时对受试者和基因进行聚类。

结果

重度OSA患者中 、 、 、 和 的表达与非重度OSA患者有显著差异,并导致免疫反应、细胞因子-细胞因子受体相互作用和核苷酸结合寡聚化结构域样受体信号通路的变化。

结论

炎症可能促成AD的发病,医生需要意识到重度OSA患者中AD的潜在发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90d5/6780075/206f863114cd/jcm-08-01361-g001.jpg

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