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Whole blood gene expression signature in patients with obstructive sleep apnea and effect of continuous positive airway pressure treatment
Respiratory Physiology & Neurobiology ( IF 2.3 ) Pub Date : 2021-07-21 , DOI: 10.1016/j.resp.2021.103746
Eva Christensson 1 , Souren Mkrtchian 2 , Anette Ebberyd 2 , Åsa Österlund Modalen 3 , Karl A Franklin 4 , Lars I Eriksson 1 , Malin Jonsson Fagerlund 1
Affiliation  

The molecular mechanisms of obstructive sleep apnea (OSA), in particular the gene expression patterns in whole blood of patients with OSA, can shed more light on the underlying pathophysiology of OSA and suggest potential biomarkers. In the current study, we have enrolled thirty patients with untreated moderate-severe OSA together with 20 BMI, age, and sex-matched controls and 15 normal-weight controls. RNA-sequencing of whole blood and home sleep apnea testing were performed in the untreated state and after three and twelve months of continuous positive airway pressure (CPAP) treatment. Analysis of the whole blood transcriptome of the patients with OSA revealed a unique pattern of differential expression with a significant number of downregulated immune-related genes including many heavy and light chain immunoglobulins and interferon-inducible genes. This was confirmed by the gene ontology analysis demonstrating enrichment with the biological processes associated with various immune functions. Expression of these genes was recovered after three months of CPAP treatment. After 12 months of CPAP treatment, the overall gene expression profile returns to the initial, untreated level. In addition, we have confirmed the importance of choosing BMI-matched controls as a reference group as opposed to normal-weight healthy individuals based on the significantly different gene expression signatures between these two groups.



中文翻译:

阻塞性睡眠呼吸暂停患者全血基因表达特征及持续气道正压治疗的效果

阻塞性睡眠呼吸暂停 (OSA) 的分子机制,特别是 OSA 患者全血中的基因表达模式,可以更多地阐明 OSA 的潜在病理生理学并提出潜在的生物标志物。在目前的研究中,我们招募了 30 名未经治疗的中重度 OSA 患者,以及 20 名 BMI、年龄和性别匹配的对照组和 15 名体重正常的对照组。在未治疗状态和连续气道正压通气 (CPAP) 治疗 3 个月和 12 个月后进行全血 RNA 测序和家庭睡眠呼吸暂停测试。对 OSA 患者全血转录组的分析揭示了一种独特的差异表达模式,其中包括大量下调的免疫相关基因,包括许多重链和轻链免疫球蛋白以及干扰素诱导基因。基因本体分析证实了这一点,该分析证明了与各种免疫功能相关的生物过程的富集。这些基因的表达在 CPAP 治疗三个月后恢复。CPAP 治疗 12 个月后,整体基因表达谱恢复到初始的未治疗水平。此外,基于这两组之间显着不同的基因表达特征,我们已经确认了选择 BMI 匹配的对照作为参考组而不是正常体重的健康个体作为参考组的重要性。基因本体分析证实了这一点,该分析证明了与各种免疫功能相关的生物过程的富集。这些基因的表达在 CPAP 治疗三个月后恢复。CPAP 治疗 12 个月后,整体基因表达谱恢复到初始的未治疗水平。此外,基于这两组之间显着不同的基因表达特征,我们已经确认了选择 BMI 匹配的对照作为参考组而不是正常体重的健康个体作为参考组的重要性。基因本体分析证实了这一点,该分析证明了与各种免疫功能相关的生物过程的富集。这些基因的表达在 CPAP 治疗三个月后恢复。CPAP 治疗 12 个月后,整体基因表达谱恢复到初始的未治疗水平。此外,基于这两组之间显着不同的基因表达特征,我们已经确认了选择 BMI 匹配的对照作为参考组而不是正常体重的健康个体作为参考组的重要性。整个基因表达谱恢复到初始的未处理水平。此外,基于这两组之间显着不同的基因表达特征,我们已经确认了选择 BMI 匹配的对照作为参考组而不是正常体重的健康个体作为参考组的重要性。整个基因表达谱恢复到初始的未处理水平。此外,基于这两组之间显着不同的基因表达特征,我们已经确认了选择 BMI 匹配的对照作为参考组而不是正常体重的健康个体作为参考组的重要性。

更新日期:2021-08-03
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