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Association of TNF-α (-308G/A) gene polymorphism with circulating TNF-α levels and excessive daytime sleepiness in adults with coronary artery disease and concomitant obstructive sleep apnea

Behboudi, Afrouz ; Thelander, Tilia ; Yazici, Duygu ; Celik, Yeliz ; Yucel-Lindberg, Tülay ; Thunström, Erik and Peker, Yüksel LU (2021) In Journal of Clinical Medicine 10(15).
Abstract

Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD), in which inflammatory activity has a crucial role. The manifestation of OSA varies significantly between individuals in clinical cohorts; not all adults with OSA demonstrate the same set of symp-toms; i.e., excessive daytime sleepiness (EDS) and/or increased levels of inflammatory biomarkers. The further exploration of the molecular basis of these differences is therefore essential for a better understanding of the OSA phenotypes in cardiac patients. In this current secondary analysis of the Randomized Intervention with Continuous Positive Airway Pressure in CAD and OSA (RICCADSA) trial (Trial Registry: ClinicalTrials.gov; No: NCT 00519597), we aimed... (More)

Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD), in which inflammatory activity has a crucial role. The manifestation of OSA varies significantly between individuals in clinical cohorts; not all adults with OSA demonstrate the same set of symp-toms; i.e., excessive daytime sleepiness (EDS) and/or increased levels of inflammatory biomarkers. The further exploration of the molecular basis of these differences is therefore essential for a better understanding of the OSA phenotypes in cardiac patients. In this current secondary analysis of the Randomized Intervention with Continuous Positive Airway Pressure in CAD and OSA (RICCADSA) trial (Trial Registry: ClinicalTrials.gov; No: NCT 00519597), we aimed to address the association of tumor necrosis factor alpha (TNF-α)-308G/A gene polymorphism with circulating TNF-α levels and EDS among 326 participants. CAD patients with OSA (apnea–hypopnea-index (AHI) ≥ 15 events/h; n = 256) were categorized as having EDS (n = 100) or no-EDS (n = 156) based on the Epworth Sleepiness Scale score with a cut-off of 10. CAD patients with no-OSA (AHI < 5 events/h; n = 70) were included as a control group. The results demonstrated no significant differences regarding the distribution of the TNF-α alleles and genotypes between CAD patients with vs. without OSA. In a multivariate analysis, the oxygen desaturation index and TNF-α genotypes from GG to GA and GA to AA as well as the TNF-α-308A allele carriage were significantly associated with the circulating TNF-α levels. Moreover, the TNF-α-308A allele was associated with a decreased risk for EDS (odds ratio 0.64, 95% confidence interval 0.41–0.99; p = 0.043) independent of age, sex, obesity, OSA severity and the circulating TNF-α levels. We conclude that the TNF-α-308A allele appears to modulate circulatory TNF-α levels and mitigate EDS in adults with CAD and concomitant OSA.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Coronary artery disease, Obstructive sleep apnea, Tumor necrosis factor
in
Journal of Clinical Medicine
volume
10
issue
15
article number
3413
publisher
MDPI AG
external identifiers
  • pmid:34362196
  • scopus:85114081185
ISSN
2077-0383
DOI
10.3390/jcm10153413
language
English
LU publication?
yes
id
b7db41fb-394b-464b-8bd1-fff70bbb7d83
date added to LUP
2021-10-05 15:11:10
date last changed
2024-04-20 12:30:54
@article{b7db41fb-394b-464b-8bd1-fff70bbb7d83,
  abstract     = {{<p>Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD), in which inflammatory activity has a crucial role. The manifestation of OSA varies significantly between individuals in clinical cohorts; not all adults with OSA demonstrate the same set of symp-toms; i.e., excessive daytime sleepiness (EDS) and/or increased levels of inflammatory biomarkers. The further exploration of the molecular basis of these differences is therefore essential for a better understanding of the OSA phenotypes in cardiac patients. In this current secondary analysis of the Randomized Intervention with Continuous Positive Airway Pressure in CAD and OSA (RICCADSA) trial (Trial Registry: ClinicalTrials.gov; No: NCT 00519597), we aimed to address the association of tumor necrosis factor alpha (TNF-α)-308G/A gene polymorphism with circulating TNF-α levels and EDS among 326 participants. CAD patients with OSA (apnea–hypopnea-index (AHI) ≥ 15 events/h; n = 256) were categorized as having EDS (n = 100) or no-EDS (n = 156) based on the Epworth Sleepiness Scale score with a cut-off of 10. CAD patients with no-OSA (AHI &lt; 5 events/h; n = 70) were included as a control group. The results demonstrated no significant differences regarding the distribution of the TNF-α alleles and genotypes between CAD patients with vs. without OSA. In a multivariate analysis, the oxygen desaturation index and TNF-α genotypes from GG to GA and GA to AA as well as the TNF-α-308A allele carriage were significantly associated with the circulating TNF-α levels. Moreover, the TNF-α-308A allele was associated with a decreased risk for EDS (odds ratio 0.64, 95% confidence interval 0.41–0.99; p = 0.043) independent of age, sex, obesity, OSA severity and the circulating TNF-α levels. We conclude that the TNF-α-308A allele appears to modulate circulatory TNF-α levels and mitigate EDS in adults with CAD and concomitant OSA.</p>}},
  author       = {{Behboudi, Afrouz and Thelander, Tilia and Yazici, Duygu and Celik, Yeliz and Yucel-Lindberg, Tülay and Thunström, Erik and Peker, Yüksel}},
  issn         = {{2077-0383}},
  keywords     = {{Coronary artery disease; Obstructive sleep apnea; Tumor necrosis factor}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{15}},
  publisher    = {{MDPI AG}},
  series       = {{Journal of Clinical Medicine}},
  title        = {{Association of TNF-α (-308G/A) gene polymorphism with circulating TNF-α levels and excessive daytime sleepiness in adults with coronary artery disease and concomitant obstructive sleep apnea}},
  url          = {{http://dx.doi.org/10.3390/jcm10153413}},
  doi          = {{10.3390/jcm10153413}},
  volume       = {{10}},
  year         = {{2021}},
}