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Low oxygen saturation during sleep reduces CD1D and RAB20 expressions that are reversed by CPAP therapy.
Sofer, Tamar; Li, Ruitong; Joehanes, Roby; Lin, Honghuang; Gower, Adam C; Wang, Heming; Kurniansyah, Nuzulul; Cade, Brian E; Lee, Jiwon; Williams, Stephanie; Mehra, Reena; Patel, Sanjay R; Quan, Stuart F; Liu, Yongmei; Rotter, Jerome I; Rich, Stephen S; Spira, Avrum; Levy, Daniel; Gharib, Sina A; Redline, Susan; Gottlieb, Daniel J.
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  • Sofer T; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA; Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA. Electronic address: t
  • Li R; Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Joehanes R; The Population Sciences Branch of the National Heart, Lung and Blood Institute, Bethesda, MD, USA and the Framingham Heart Study, Framingham, MA, USA; Hebrew SeniorLife, Harvard Medical School, Boston, MA, USA.
  • Lin H; The Population Sciences Branch of the National Heart, Lung and Blood Institute, Bethesda, MD, USA and the Framingham Heart Study, Framingham, MA, USA; Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
  • Gower AC; Clinical and Translational Science Institute, Boston University School of Medicine, Boston, USA.
  • Wang H; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA; Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Kurniansyah N; Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Cade BE; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA; Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Lee J; Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Williams S; Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Mehra R; Neurologic Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Patel SR; Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
  • Quan SF; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA; Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Liu Y; Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
  • Rotter JI; The Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Rich SS; Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
  • Spira A; Boston University School of Medicine and Boston Medical Center, Boston, MA, USA.
  • Levy D; The Population Sciences Branch of the National Heart, Lung and Blood Institute, Bethesda, MD, USA and the Framingham Heart Study, Framingham, MA, USA.
  • Gharib SA; Computational Medicine Core, Center for Lung Biology, University of Washington Medicine Sleep Center, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, WA, USA.
  • Redline S; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA; Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Computational Medicine Core, Center for Lung Biology, University of Washington Medicine Sleep Center, Division
  • Gottlieb DJ; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA; Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
EBioMedicine ; 56: 102803, 2020 Jun.
Article en En | MEDLINE | ID: mdl-32512511
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes de la Apnea del Sueño / Oxihemoglobinas / Regulación hacia Abajo / Proteínas de Unión al GTP rab / Presión de las Vías Aéreas Positiva Contínua / Antígenos CD1d Tipo de estudio: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: EBioMedicine Año: 2020 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes de la Apnea del Sueño / Oxihemoglobinas / Regulación hacia Abajo / Proteínas de Unión al GTP rab / Presión de las Vías Aéreas Positiva Contínua / Antígenos CD1d Tipo de estudio: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: EBioMedicine Año: 2020 Tipo del documento: Article Pais de publicación: Países Bajos