ArticleChest2013
Endothelial dysfunction in children with obstructive sleep apnea is associated with epigenetic changes in the eNOS gene.
Article in Chest, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 4 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 4 syntheses or guidelines pooled it, 89 citations in OpenAlex.
- Advancements in pediatric obstructive sleep apnea: cognitive implications and the role of AI in precision medicine.Frontiers in medicine · 2025Pooled it
- Epigenetics of obstructive sleep apnea syndrome: a systematic review.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2021Pooled it
- Effects of early- and mid-life stress on DNA methylation of genes associated with subclinical cardiovascular disease and cognitive impairment: a systematic review.BMC medical genetics · 2019Pooled it
- Pooled it
- Pediatric OSA-Spectrum of the Disease and Opportunities for Personalized Interventions.Journal of personalized medicine · 2026Review
- Intermittent Hypoxia Mimicking Sleep Apnea Induces Systemic and Tissue Specific Epigenetic Changes and p16-Mediated Cellular Senescence Underlying Vascular Dysfunction.Research square · 2026Article
- Research on Large Endothelial Cell-Derived Extracellular Vesicles in Pediatric Obstructive Sleep Apnea Syndrome.Nature and science of sleep · 2026Article
- Cardiovascular complications in children with Down syndrome and sleep disordered breathing.Paediatric respiratory reviews · 2025Review
- Epigenetic alterations in obstructive sleep Apnea: a pooled analysis of DNA methylation profiles in humans and animal models.Clinical epigenetics · 2025Article
- The Link Between Sleep-Related Breathing Disorders and Idiopathic Pulmonary Fibrosis: Pathophysiological Mechanisms and Treatment Options-A Review.Journal of clinical medicine · 2025Review
- Unveiling the molecular and cellular links between obstructive sleep apnea-hypopnea syndrome and vascular aging.Chinese medical journal · 2025Review
- Article
- Oxidative stress and optical coherence tomography angiography evaluation of choriocapillaris and retinal vessel density in children with obstructive sleep apnea.Sleep & breathing = Schlaf & Atmung · 2024Article
- Murine Pro-Inflammatory Responses to Acute and Sustained Intermittent Hypoxia: Implications for Obstructive Sleep Apnea Research.The Laryngoscope · 2024Article
- Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome.Signal transduction and targeted therapy · 2023Review
- The Influence of Comorbidities on Chemokine and Cytokine Profile in Obstructive Sleep Apnea Patients: Preliminary Results.Journal of clinical medicine · 2023Article
- Advances in Molecular Pathology of Obstructive Sleep Apnea.Molecules (Basel, Switzerland) · 2022Review
- On the Relationship between Diabetes and Obstructive Sleep Apnea: Evolution and Epigenetics.Biomedicines · 2022Review
- Extracellular Vesicles Derived from Intermittent Hypoxia-Treated Red Blood Cells Impair Endothelial Function Through Regulating eNOS Phosphorylation and ET-1 Expression.Cardiovascular drugs and therapy · 2021Article
- The Genetics of Sleep Disorders in Children: A Narrative Review.Brain sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundObstructive sleep apnea (OSA) is a highly prevalent disorder that has been associated with an increased risk for cardiovascular morbidity, even in children. However, not all children with OSA manifest alterations in endothelial postocclusive hyperemia, an endothelial nitric oxide synthase (eNOS)-dependent response. Since expression of the eNOS gene is regulated by epigenetic mechanisms and OSA may cause epigenetic modifications such as DNA hypermethylation, we hypothesized that epigenetic modifications in the eNOS gene may underlie the differential vascular phenotypes in pediatric OSA.
methodsAge-, sex-, ethnicity-, and BMI-matched prepubertal children with polysomnographically confirmed OSA and either normal (OSAn) or abnormal (OSAab) postocclusive hyperemic responses, assessed as the time to attain peak reperfusion flow (Tmax) by laser Doppler flowmetry, were recruited. Blood genomic DNA was assessed for epigenetic modifications in the eNOS gene using pyrosequencing. Children with no evidence of OSA or endothelial dysfunction served as a control group.
resultsThe study comprised 36 children with OSA (11 with OSAab and 25 with OSAn) and 35 children in the control group. Overall, the mean age was 7.5 ± 2.4 years, 65% were boys, and 30% were obese; mean apnea-hypopnea index was 18 ± 8.6/h of sleep for the children with OSA. Tmax was 66.7 ± 8.8 s in the OSAab group and 30.1 ± 8.3 s in the OSAn group (P < .001). Pyrosequencing of the proximal promoter region of the eNOS gene revealed no significant differences in six of the seven CpG sites. However, a CpG site located at position -171 (relative to transcription start site), approximating important transcriptional elements, displayed significantly higher methylation levels in the OSAab group as compared with the OSAn or control groups (81.5% ± 3.5%, 74.8% ± 1.4%, and 74.5% ± 1.7%, respectively; P < .001). eNOS mRNA expression levels were assessed in a separate group of children and were significantly reduced in the OSAab group in comparison with the OSAn group.
conclusionsThe presence of abnormal eNOS-dependent vascular responses in children with OSA is associated with epigenetic modifications in the eNOS gene.
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Registered trials
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