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

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 symptoms; 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-alpha)-308G/A gene polymorphism with circulating TNF-alpha 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-alpha alleles and genotypes between CAD patients with vs. without OSA. In a multivariate analysis, the oxygen desaturation index and TNF-alpha genotypes from GG to GA and GA to AA as well as the TNF-alpha-308A allele carriage were significantly associated with the circulating TNF-alpha levels. Moreover, the TNF-alpha-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-alpha levels. We conclude that the TNF-alpha-308A allele appears to modulate circulatory TNF-alpha levels and mitigate EDS in adults with CAD and concomitant OSA.