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在伴有阻塞性睡眠呼吸障碍的儿童的 EBV+扁桃体中下调。

Is Downregulated in EBV+ Tonsils of Children with Obstructive Sleep-Disordered Breathing.

机构信息

Department of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Department of Pediatric Otolaryngology, Children's Hospital Colorado, Aurora, CO 80045, USA.

出版信息

Genes (Basel). 2024 Oct 14;15(10):1324. doi: 10.3390/genes15101324.

DOI:10.3390/genes15101324
PMID:39457448
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11507010/
Abstract

Obstructive sleep-disordered breathing (oSDB) is a heterogeneous phenotype that is increasing in prevalence worldwide and has many potential comorbidities that could severely affect quality of life. There is a need to identify biomarkers for oSDB and its comorbidities to improve clinical management, particularly in children. We performed bulk mRNA-sequencing, differential expression analysis, and qPCR replication of selected differentially expressed genes (DEGs) using RNA samples extracted from tonsils of children with oSDB. Two variables were used as classifier, namely, detection of Epstein-Barr virus (EBV) in tonsils and need for continuous positive airway pressure (CPAP) treatment. Standard statistical tests were used to determine associations across clinical, EBV, and DEG variables. Nineteen genes were dysregulated in tonsils that are EBV+ or from children needing CPAP. Of these genes, was downregulated in both EBV+ and CPAP+ tonsils, and this downregulation was replicated by qPCR in an independent set of pediatric samples. In the tonsils of adult patients with oSDB, was positively correlated with age, and potentially with diastolic blood pressure. Taken together, and DEGs in tonsillar tissues may be useful as potential biomarkers of oSDB severity and comorbidity across the lifespan, with levels being dependent on latent EBV infection.

摘要

阻塞性睡眠呼吸障碍(OSDB)是一种表型异质性疾病,在全球范围内的患病率不断增加,并且有许多潜在的合并症,这些合并症可能严重影响生活质量。因此,需要识别 OSDB 及其合并症的生物标志物,以改善临床管理,特别是在儿童中。

我们使用从患有 OSDB 的儿童扁桃体中提取的 RNA 样本进行了批量 mRNA 测序、差异表达分析和选定差异表达基因(DEG)的 qPCR 复制。使用两个变量作为分类器,即扁桃体中是否检测到 EBV 和是否需要持续气道正压通气(CPAP)治疗。使用标准统计检验来确定 across 临床、EBV 和 DEG 变量之间的关联。

在 EBV+或需要 CPAP 治疗的儿童的扁桃体中,有 19 个基因失调。这些基因中,在 EBV+和 CPAP+的扁桃体中均下调,并且在一组独立的儿科样本中通过 qPCR 复制了这种下调。在患有 OSDB 的成年患者的扁桃体中,与年龄呈正相关,并且可能与舒张压呈正相关。

总之,扁桃体组织中的 和 DEG 可能是 OSDB 严重程度和整个生命周期合并症的有用生物标志物, 水平取决于潜伏性 EBV 感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bec2/11507010/0c60ddd89fc9/genes-15-01324-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bec2/11507010/a357ef3f9db8/genes-15-01324-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bec2/11507010/0c60ddd89fc9/genes-15-01324-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bec2/11507010/a357ef3f9db8/genes-15-01324-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bec2/11507010/0c60ddd89fc9/genes-15-01324-g002.jpg

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本文引用的文献

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Palate shape is associated with Unilateral Hypoglossal Nerve Stimulation Outcomes.腭形状与单侧舌下神经刺激的结果有关。
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Genome-wide association study of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sex.在百万退伍军人计划中进行的全基因组关联研究揭示了性别导致的阻塞性睡眠呼吸暂停的遗传异质性。
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Adherence to Continuous Positive Airway Pressure Therapy in Pediatric Patients with Obstructive Sleep Apnea: A Meta-Analysis.小儿阻塞性睡眠呼吸暂停患者持续气道正压通气治疗的依从性:一项荟萃分析。
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International Consensus Statement on Obstructive Sleep Apnea.国际阻塞性睡眠呼吸暂停共识声明。
Int Forum Allergy Rhinol. 2023 Jul;13(7):1061-1482. doi: 10.1002/alr.23079. Epub 2023 Mar 30.
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