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Published on: December 6, 2016
TNF-α gene polymorphisms and excessive daytime sleepiness in pediatric obstructive sleep apnea
Abdelnaby Khalyfa1, Laura D Serpero, Leila Kheirandish-Gozal
1Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, University of Chicago, Chicago, IL, USA.
Insights
Obstructive sleep apnea (OSA) in children is linked to higher tumor necrosis factor-alpha (TNF-α) levels and sleepiness, especially with the TNF-α -308G gene variant. This genetic factor may explain sleepiness variability in pediatric OSA.
Area of Science:
- Pediatric Sleep Medicine
- Immunogenetics
- Molecular Biology
Background:
- Obstructive sleep apnea (OSA) is a common pediatric disorder.
- Tumor necrosis factor-alpha (TNF-α) is an inflammatory cytokine implicated in various conditions.
- Genetic variations in inflammatory pathways may influence OSA severity and symptoms.
Purpose of the Study:
- To investigate the relationship between sleepiness, TNF-α plasma levels, and TNF-α gene polymorphisms in children with OSA.
- To determine if specific TNF-α gene variants are associated with increased sleepiness or elevated TNF-α levels in pediatric OSA.
Main Methods:
- A case-control study involving children evaluated for OSA (n=60) and matched controls (n=80).
- Assessment of sleepiness using the modified Epworth Sleepiness Scale (ESS).
- Measurement of TNF-α plasma concentrations via ELISA and genotyping of TNF-α single nucleotide polymorphisms (SNPs) using real-time PCR.
Main Results:
- Children with OSA exhibited higher morning TNF-α levels and ESS scores compared to controls.
- Significant variability in TNF-α levels and sleepiness was observed within the OSA group.
- The TNF-α -308G gene polymorphism was strongly associated with increased TNF-α plasma levels and excessive daytime sleepiness in children with OSA.
Conclusions:
- Elevated TNF-α levels and increased sleepiness are present in a subset of children with OSA.
- The TNF-α -308G polymorphism is a key factor contributing to increased TNF-α and sleepiness in pediatric OSA.
- Genetic variations, specifically the TNF-α -308G SNP, may explain the considerable variability in excessive daytime sleepiness observed in pediatric OSA.
Objective:
To assess sleepiness, TNF-α plasma levels, and genomic variance in the TNF-α gene in children with obstructive sleep apnea (OSA).
Study Design:
Children being evaluated for OSA (n = 60) and matched control children (n = 80) were assessed with a modified Epworth Sleepiness Scale questionnaire and underwent a blood draw the morning after nocturnal polysomnography. TNF-α plasma concentrations were assayed using ELISA, and genomic DNA was extracted. Genotyping and allelic frequencies were determined for 4 TNF-α single nucleotide polymorphisms using real-time polymerase chain reaction genotyping assays.
Results:
Morning TNF-α levels and Epworth Sleepiness Scale scores were increased in the presence of OSA, but substantial variability was present. Although TNF-α plasma concentrations were globally increased in OSA, most of the variance was attributable to the presence or absence of TNF-α -308G gene polymorphism.
Conclusions:
TNF-α levels are increased in a subset of children with OSA, particularly among those harboring the TNF-α -308G single nucleotide polymorphism. Among the latter, significant increases in excessive daytime sleepiness symptoms are also present. The relatively high variability of excessive daytime sleepiness in pediatric OSA may be related to underlying TNF-α gene polymorphisms, particularly -308G.
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