0021 Lower Oxygen Saturation During Sleep Is Associated With Reduced Expressions Of Cd1d And Rab20 That Is Potentially Reversed By CPAP Therapy

Abstract

Rationale: Obstructive Sleep Apnea (OSA) is associated with a wide range of physiological changes, many of which are considered secondary to overnight hypoxemia, with substantial inter-individual differences. A source for OSA-related physiological effects may relate to the influence of hypoxia on gene expression. While prior research demonstrated that OSA is associated with gene expression in blood, studies were only in small, clinic based samples. Here we study OSA-related gene expression associations in large population-based studies, and in a small sample of individuals with OSA before and after treatment using continuous positive airway pressure (CPAP) who participated in the Heart Biomarkers in Apnea Treatment Study (HeartBEAT). Methods: We performed discovery analysis and then cross-cohort and metaanalysis in two population-based studies: the Multi-Ethnic Study of Atherosclerosis (MESA; N = 580), and the Framingham Heart Study (FHS; N=571). We studied the association of gene expression in blood with three correlated traits that characterize the severity of OSA in different ways: the Apnea Hypopnea Index (AHI), defined as the number of apnea and hypopnea events accompanied by oxygen desaturation of at least 3% experienced per hour of sleep; average oxygen saturation (AveO2); and minimum oxygen saturation (minO2) during sleep. Associations with FDR q-value<0.05 in one study and p-value<0.05 in the other study were determined to have replicated. Associations that replicated between FHS and MESA, or with FDR qvalue< 0.05 in a meta-analysis, were carried forward for gene expression analysis in the blood of 15 participants from the HeartBEAT study who had moderate or severe OSA and were studied before and after three months of treatment with CPAP. In addition, we performed pathway analysis using GOrilla, in both FHS and MESA separately, using genes with p-values<0.001. Results: we identified 22 genes associated with OSA traits in both MESA and FHS, with most associations observed in AveO2 and minO2 Two of these genes further showed evidence of change with treatment in HeartBEAT: lower CD1D and RAB20 expressions were associated with lower average oxygen saturation in MESA and FHS, and CPAP treatment increased their expression in HeartBEAT. Pathway analysis detected cardiac-activity related pathways in FHS, oxygen response pathways, and more. Conclusions: We identified gene expressions changes associated with OSA traits and that appear to respond to CPAP therapy: CD1D, which encodes the CD1d antigen, and is associated with autoimmune diseases; and RAB20, a GTPase enzyme which is a Hypoxia-inducible transcription factor (HIF) target.