Association of TNF-a (-308G/A) Gene Polymorphism with Changes in Circulating TNF-a Levels in Response to CPAP Treatment in Adults with Coronary Artery Disease and Obstructive Sleep Apnea

Rationale: We recently demonstrated that patients with coronary artery disease (CAD) and obstructive sleep apnea (OSA) carrying the tumor necrosis factor-alpha (TNF- a) A allele had increased circulating TNF-alpha levels compared with the ones carrying the TNF-alpha G allele. In the current study, we addressed the effect of TNF-alpha (-308G/A) gene polymorphism on circulating TNF-alpha levels following continuous positive airway pressure (CPAP) therapy. Methods: This study was a secondary analysis of the RICCADSA trial (NCT00519597) conducted in Sweden. CAD patients with OSA (apnea-hypopnea index) of >= 15 events/h and an Epworth Sleepiness Scale (ESS) score of <10 were randomized to CPAP or no-CPAP groups, and OSA patients with an ESS score of >= 10 were offered CPAP treatment. Blood samples were obtained at baseline and 12-month follow-up visits. TNF-alpha was measured by immunoassay (Luminex, R&D Systems). Genotyping of TNF-alpha-308G/A (single nucleotide polymorphism Rs1800629) was performed by polymerase chain reaction-restriction fragment length polymorphism. Results: In all, 239 participants (206 men and 33 women; mean age 64.9 (SD 7.7) years) with polymorphism data and circulating levels of TNF-alpha at baseline and 1-year follow-up visits were included. The median circulating TNF-alpha values fell in both groups between baseline and 12 months with no significant within- or between-group differences. In a multivariate linear regression model, a significant change in circulating TNF-alpha levels from baseline across the genotypes from GA to GA and GA to AA (standardized fi-coefficient 0.129, 95% confidence interval (CI) 1.82; 0.12; p = 0.025) was observed in the entire cohort. The association was more pronounced among the individuals who were using the device for at least 4 h/night (n = 86; standardized fi-coefficient 2.979 (95% CI 6.11; 1.21); p = 0.004)), whereas no significant association was found among the patients who were non-adherent or randomized to no-CPAP. The participants carrying the TNF-alpha A allele were less responsive to CPAP treatment regarding the decline in circulating TNF-alpha adherence (standardized fi-coefficient 0.212, (95% CI 5.66; 1.01); p = 0.005). Conclusions: Our results suggest that TNF- a (-308G/A) gene polymorphism is associated with changes in circulating TNF-alpha levels in response to CPAP treatment in adults with CAD and OSA.