Whole blood gene expression signature in patients with obstructive sleep apnea and effect of continuous positive airway pressure treatment.

The molecular mechanisms of obstructive sleep apnea (OSA), in particular the gene expression patterns in whole blood of patients with OSA, can shed more light on the underlying pathophysiology of OSA and suggest potential biomarkers. In the current study, we have enrolled thirty patients with untreated moderate-severe OSA together with 20 BMI, age, and sex-matched controls and 15 normal-weight controls. RNA-sequencing of whole blood and home sleep apnea testing were performed in the untreated state and after three and twelve months of continuous positive airway pressure (CPAP) treatment. Analysis of the whole blood transcriptome of the patients with OSA revealed a unique pattern of differential expression with a significant number of downregulated immune-related genes including many heavy and light chain immunoglobulins and interferon-inducible genes. This was confirmed by the gene ontology analysis demonstrating enrichment with the biological processes associated with various immune functions. Expression of these genes was recovered after three months of CPAP treatment. After 12 months of CPAP treatment, the overall gene expression profile returns to the initial, untreated level. In addition, we have confirmed the importance of choosing BMI-matched controls as a reference group as opposed to normal-weight healthy individuals based on the significantly different gene expression signatures between these two groups.