Xinjiang Medical University, Urumqi, 830001 Xinjiang, China.
Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, National Health Committee Key Laboratory of Hypertension Clinical Research, Urumqi, 830001 Xinjiang, China.
Biomed Res Int. 2021 Feb 18;2021:6656943. doi: 10.1155/2021/6656943. eCollection 2021.
Obstructive sleep apnea (OSA) is a prevalent chronic disease that increases the risk of cardiovascular disease and metabolic and neuropsychiatric disorders, resulting in a considerable socioeconomic burden. The present study was aimed at identifying potential key genes influencing the mechanisms and consequences of OSA.
Gene expression profiles associated with OSA were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in subcutaneous adipose tissues from patients with OSA and normal tissues were screened using R software, followed by gene ontology and pathway enrichment analyses. Subsequently, a protein-protein interaction (PPI) network was constructed and hub genes were extracted using Cytoscape plugins. The intersected core genes derived from different topological algorithms were considered hub genes, and the potential candidate gene was selected from them for further analyses of expression variations using another GEO dataset and targeted capture sequencing in 100 subjects (50 with severe OSA and 50 without OSA).
A total of 373 DEGs were identified in OSA samples relative to normal controls, which were primarily associated with olfactory transduction and neuroactive ligand-receptor interaction. Upon analyses of nine topological algorithms and available literature, we finally focused on glial cell-derived neurotrophic factor (GDNF) as the candidate gene and validated its low expression in OSA samples. Two rare nonsynonymous variants (p.D56N and p.R93Q) were identified among the 100 cases through targeted sequencing of GDNF, which could be potentially deleterious based on pathogenicity prediction programs; however, no significant association was detected in single nucleotide polymorphisms.
The present study identified GDNF as a promising candidate gene for OSA and its two rare and potentially deleterious mutations through a combination of bioinformatics and targeted capture sequencing analyses.
阻塞性睡眠呼吸暂停（OSA）是一种普遍存在的慢性疾病，会增加心血管疾病以及代谢和神经精神障碍的风险，造成相当大的社会经济负担。本研究旨在确定影响 OSA 机制和后果的潜在关键基因。
从基因表达综合数据库（GEO）中获取与 OSA 相关的基因表达谱。使用 R 软件筛选 OSA 患者和正常组织的皮下脂肪组织中的差异表达基因（DEGs），然后进行基因本体论和途径富集分析。随后，使用 Cytoscape 插件构建蛋白质-蛋白质相互作用（PPI）网络并提取枢纽基因。不同拓扑算法得出的交集核心基因被认为是枢纽基因，从中选择潜在的候选基因，然后使用另一个 GEO 数据集和 100 名受试者（50 名严重 OSA 患者和 50 名无 OSA 患者）的靶向捕获测序来分析其表达变化。
与正常对照组相比，OSA 样本中总共鉴定出 373 个 DEGs，这些基因主要与嗅觉转导和神经活性配体-受体相互作用有关。通过对 9 种拓扑算法和现有文献进行分析，我们最终将胶质细胞源性神经营养因子（GDNF）作为候选基因，并验证了其在 OSA 样本中的低表达。通过 GDNF 的靶向测序，在 100 例病例中发现了两种罕见的非同义突变（p.D56N 和 p.R93Q），根据致病性预测程序，这些突变可能具有潜在的有害性；然而，在单核苷酸多态性中没有检测到显著的相关性。
本研究通过生物信息学和靶向捕获测序分析相结合，确定 GDNF 是 OSA 的一个有前途的候选基因，其两个罕见且潜在有害的突变可能与 OSA 有关。
