Association of TNF-α (-308G/A) Gene Polymorphism with Changes in Circulating TNF-α 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 allele had increased circulating levels compared with the ones carrying the allele. In the current study, we addressed the effect of (-308G/A) gene polymorphism on circulating 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. was measured by immunoassay (Luminex, R&D Systems). Genotyping of -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 at baseline and 1-year follow-up visits were included. The median circulating 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 levels from baseline across the genotypes from GA to GA and GA to AA (standardized β-coefficient -0.129, 95% confidence interval (CI) -1.82; -0.12; = 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 β-coefficient -2.979 (95% CI -6.11; -1.21); = 0.004)), whereas no significant association was found among the patients who were non-adherent or randomized to no-CPAP. The participants carrying the allele were less responsive to CPAP treatment regarding the decline in circulating despite CPAP adherence (standardized β-coefficient -0.212, (95% CI -5.66; -1.01); = 0.005).

CONCLUSIONS

Our results suggest that (-308G/A) gene polymorphism is associated with changes in circulating levels in response to CPAP treatment in adults with CAD and OSA.