Dissection of Differentially Expressed Genes and Pathways in Patients With Obstructive Sleep Apnea Syndrome Before and After CPAP Treatment

Obstructive sleep apnea syndrome (OSAS) is characterized with recurrent collapse of upper airway during sleep and resulted in hypoxia and sleep fragmentation, which resulted in cardiovascular diseases, metabolic disorders and neurocognitive dysfunctions. The cardiovascular complications attributed to OSAS included hypertension, coronary artery disease, heart failure and stroke. The mechanisms responsible for developments of cardiovascular sequelae included repeated episodes of hypoxia and hypercapnia, exaggerated negative intrathoracic pressure and bursts of sympathetic activity provoking surges in blood pressure and heart rate. Increase of inflammatory mediators, which included C-reactive protein, oxidative stress, adhesion molecules, vascular endothelial growth factor and proinflammatory cytokines, were thought to involve in the developments of cardiovascular diseases in patients with OSAS.

To clarify the exact mechanisms of OSAS and the linkage to cardiovascular complications, in our previous study, we used oligo microarray to genome-wide profile the gene expression patterns in OSAS patients and the changes of gene expressions before and after four-week CPAP treatment. The oligo-microarray data were processed with CRSD database and two-way hierarchical clustering method. The results showed the gene expression patterns were different between control subjects and OSA patients and CPAP treatment also altered the gene expression patterns. Totally 27 genes and four pathways were identified as target genes and pathways from comparing the gene pattern changes before and after CPAP treatment, which included apoptosis, oxidative phosphorylation, cell adhesion and activation and metabolism. To continue analyzing the gene pattern changes before and after CPAP treatment, we propose this three-year project to achieve the following goals: (1) To verify the differentially expressed genes and pathways between normal and OSA patients, and OSA patients before and after CPAP treatment. (2) To correlate the confirmed genes with the clinical presentations and CPAP effects in another 50 OSAS subjects to validate the altered gene expressions and pathways involved. (3) To establish a cell model to investigate the differentially expressed genes and the putative biological pathways involved in OSA syndrome. The information obtained by this approach is very useful to understand the pathogenic mechanism of OSA that leads to systemic complications and further therapeutic intervention may therefore be possible.