Low oxygen saturation during sleep reduces CD1D and RAB20 expressions that are reversed by CPAP therapy.

Journal Article (Journal Article;Multicenter Study)

BACKGROUND: Sleep Disordered Breathing (SDB) is associated with a wide range of pathophysiological changes due, in part, to hypoxemia during sleep. We sought to identify gene transcription associations with measures of SDB and hypoxemia during sleep, and study their response to treatment. METHODS: In two discovery cohorts, Framingham Offspring Study (FOS; N = 571) and the Multi-Ethnic Study of Atherosclerosis (MESA; N = 580), we studied gene expression in peripheral blood mononuclear cells in association with three measures of SDB: Apnea Hypopnea Index (AHI); average oxyhemoglobin saturation (avgO2) during sleep; and minimum oxyhemoglobin saturation (minO2) during sleep. Associated genes were used for analysis of gene expression in the blood of 15 participants with moderate or severe obstructive sleep apnea (OSA) from the Heart Biomarkers In Apnea Treatment (HeartBEAT) trial. These genes were studied pre- and post-treatment (three months) with continuous positive airway pressure (CPAP). We also performed Gene Set Enrichment Analysis (GSEA) on all traits and cohort analyses. FINDINGS: Twenty-two genes were associated with SDB traits in both MESA and FOS. Of these, lower expression of CD1D and RAB20 was associated with lower avgO2 in MESA and FOS. CPAP treatment increased the expression of these genes in HeartBEAT participants. Immunity and inflammation pathways were up-regulated in subjects with lower avgO2; i.e., in those with a more severe SDB phenotype (MESA), whereas immuno-inflammatory processes were down-regulated following CPAP treatment (HeartBEAT). INTERPRETATION: Low oxygen saturation during sleep is associated with alterations in gene expression and transcriptional programs that are partially reversed by CPAP treatment.

Full Text

Duke Authors

Cited Authors

  • Sofer, T; Li, R; Joehanes, R; Lin, H; Gower, AC; Wang, H; Kurniansyah, N; Cade, BE; Lee, J; Williams, S; Mehra, R; Patel, SR; Quan, SF; Liu, Y; Rotter, JI; Rich, SS; Spira, A; Levy, D; Gharib, SA; Redline, S; Gottlieb, DJ

Published Date

  • June 2020

Published In

Volume / Issue

  • 56 /

Start / End Page

  • 102803 -

PubMed ID

  • 32512511

Pubmed Central ID

  • PMC7276515

Electronic International Standard Serial Number (EISSN)

  • 2352-3964

Digital Object Identifier (DOI)

  • 10.1016/j.ebiom.2020.102803

Language

  • eng

Conference Location

  • Netherlands