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DNA methylation profiling in blood of OSA patients and controls

ABSTRACT: Obstructive sleep apnea (OSA) is associated with increased risk for cardiovascular morbidity and mortality. Epidemiological and animal models studies generate hypotheses for innovative strategies in OSA management by interfering intermediates mechanisms associated with cardiovascular complications. In this study, we interrogated DNA methylation profiles in 16 polysomnographically evaluated OSA patients (Apnea Hypopnea Index, AHI > 30) and 8 controls (AHI<5 events/h sleep). Blood samples were collected at initial visit (V1) and a year later (V2). OSA patients received Continuous Positive Air Pressure (CPAP) therapy with high adherence (> 4 hours/night). Control individuals did not receive CPAP therapy. Genomic DNA was treated with sodium bisulfite. Converted DNA was analyzed using Illumina’s Infinium Human Methylation 450 BeadChip assay. DNA methylation profiles enabled the prospective evaluation of inflammatory and epigenetics mechanism involved in cardiovascular complication of OSA patients compared with non OSA subjects, as well as the variation of epigenetic profiles in OSA patients after one year of high-adherence CPAP therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE190164 | GEO | 2022/11/04

REPOSITORIES: GEO

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Effects of CPAP Therapy on Leukocyte Gene Expression

Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with a number of chronic disorders that may improve with effective therapy. However, the molecular pathways affected by continuous positive airway pressure (CPAP) treatment are largely unknown. We sought to assess the system-wide consequences of CPAP therapy by transcriptionally profiling peripheral blood leukocytes (PBLs). Methods: Subjects diagnosed with severe OSA were treated with CPAP, and whole-genome expression measurement of PBLs was performed at baseline and following therapy. We used Gene Set Enrichment Analysis (GSEA) to identify gene sets that were differentially enriched. Network analysis was then applied to identify key drivers of pathways influenced by CPAP. Results: 18 subjects with severe OSA (apnea hypopnea index ≥ 30 events/hour) underwent CPAP therapy and microarray analysis of their PBLs. Treatment with CPAP improved AHI, daytime sleepiness and blood pressure but did not affect anthropometric measures. GSEA revealed a number of enriched gene sets, many of which were involved in neoplastic processes and displayed down-regulated expression patterns in response to CPAP. Network analysis identified several densely connected genes that are important modulators of cancer and tumor growth. Conclusions: Effective therapy of OSA with CPAP is associated with alterations in circulating leukocyte gene expression. Functional enrichment and network analyses highlighted transcriptional suppression in cancer-related pathways suggesting potentially novel mechanisms linking OSA with neoplastic signatures. Total RNA from peripheral blood leukocytes of 18 subjects with severe sleep apnea at baseline and after effective CPAP therapy was hybridized to 36 Affymetrix Genechip Human Gene 1.0 ST microarrays

2013-12-31 | E-GEOD-49800 | biostudies-arrayexpress

Effects of CPAP Therapy on Leukocyte Gene Expression

2013-12-31 | GSE49800 | GEO

Subcutaneous fat transcriptome in obstructive sleep apnea and after treatment with CPAP

Project description:Obstructive sleep apnea (OSA) has been linked to dysregulated metabolic states and treatment of sleep apnea may improve these conditions. Subcutaneous adipose tissue is a readily samplable fat depot that plays an important role in regulating metabolism. However, neither the pathophysiologic consequences of OSA nor the effects of continuous positive airway pressure (CPAP) in altering this compartment’s molecular pathways are understood. This study aimed to systematically identify subcutaneous adipose tissue transcriptional programs modulated in OSA and in response to its effective treatment with CPAP. Two subject groups were investigated: Study Group 1 was comprised of 10 OSA and 8 controls; Study Group 2 included 24 individuals with OSA studied at baseline and following CPAP. For each subject, genome-wide gene expression measurement of subcutaneous fat was performed. Differentially activated pathways elicited by OSA (Group 1) and in response to its treatment (Group 2) were determined using network and Gene Set Enrichment Analysis (GSEA). In Group 2, treatment of OSA with CPAP improved apnea hypopnea index, daytime sleepiness, and blood pressure, but not anthropometric measures. In Group 1, GSEA revealed many up-regulated gene sets in OSA subjects, most of which were involved in immuno-inflammatory (e.g., interferon-γ signaling), transcription, and metabolic processes such as adipogenesis. Unexpectedly, CPAP therapy in Group 2 subjects was also associated with up-regulation of several immune pathways as well as cholesterol biosynthesis. Collectively, our findings demonstrate that OSA alters distinct inflammatory and metabolic programs in subcutaneous fat, but these transcriptional signatures are not reversed with short-term effective therapy.

2019-12-21 | GSE135917 | GEO

Obstructive sleep apnea is related to alterations in intestinal microbiome and impaired intestinal barrier function

Project description:Objectives: Obstructive Sleep Apnea (OSA) is related to repeated upper airway collapse, intermittent hypoxia, and intestinal barrier dysfunction. The resulting damage to the intestinal barrier may affect or be affected by the intestinal microbiota. Methods: A prospective case-control was used, including 48 subjects from Sleep Medicine Center of Nanfang Hospital. Sleep apnea was diagnosed by overnight polysomnography. Fecal samples and blood samples were collected from subjects to detect intestinal microbiome composition (by 16S rDNA gene amplification and sequencing) and intestinal barrier biomarkers – intestinal fatty acid-binding protein (I-FABP) and D-lactic acid (D-LA) (by ELISA and colorimetry, respectively). Results: The severity of OSA was related to differences in the structure and composition of the intestinal microbiome. Enriched Fusobacterium, Megamonasa, Lachnospiraceae_UCG_006, and reduced Anaerostipes was found in patients with severe OSA. Enriched Ruminococcus_2, Lachnoclostridium, Lachnospiraceae_UCG_006, and Alloprevotella was found in patients with high intestinal barrier biomarkers. Lachnoclostridium and Lachnospiraceae_UCG_006 were the common dominant bacteria of OSA and intestinal barrier damage. Fusobacterium and Peptoclostridium was independently associated with apnea-hypopnea index (AHI). The dominant genera of severe OSA were also related to glucose, lipid, neutrophils, monocytes and BMI. Network analysis identified links between the intestinal microbiome, intestinal barrier biomarkers, and AHI. Conclusions: The study confirms that changes in the intestinal microbiota are related to intestinal barrier biomarkers among patients in OSA. These changes may play a pathophysiological role in the systemic inflammation and metabolic comorbidities associated with OSA, leading to multi-organ morbidity of OSA.

2023-08-30 | GSE181270 | GEO

Transcriptional survey of peripheral blood links lower oxygen saturation during sleep with reduced expressions of CD1D and RAB20 that is reversed by CPAP therapy

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2020-06-16 | GSE133601 | GEO

Microarray gene expression profiles of peripheral blood mononuclear cells (PBMC) in patients with obstructive sleep apnea and primary snoring

Project description:Therefore, we extended our investigation into OSA patients with long-term continuous positive airway pressure (CPAP) treatment, hypertension, or excessive daytime sleepiness (EDS) by analyzing whole-genome gene expression profiles of PBMC in three comparisons: (1) treatment-naÃ¯ve moderate to very severe OSA patients versus subjects with primary snoring; (2) moderate to very severe OSA patients with hypertension or EDS versus those without hypertension or EDS, respectively; (3) treatment-naÃ¯ve very severe OSA patients versus those receiving at least one year of adequate CPAP treatment. We analyzed whole-genome gene expression profiles of peripheral blood mononuclear cells from 48 patients with sleep-disordered breathing stratified into four groups: primary snoring (PS), moderate to severe OSA (MSO), very severe OSA (VSO), and very severe OSA patients with long-term continuous positive airway pressure (CPAP) treatment (VSOC).

2015-12-31 | E-GEOD-75097 | biostudies-arrayexpress

Epigenome analysis of peripheral blood mononuclear cell (PBMC) samples from obstructive sleep apnea patients and healthy subjects

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2015-12-31 | GSE61463 | GEO

Epigenome analysis of peripheral blood mononuclear cell (PBMC) samples from obstructive sleep apnea patients and healthy subjects

2015-12-31 | E-GEOD-61463 | biostudies-arrayexpress

Intermittent Hypoxia Alters Gene Expression in Peripheral Blood Mononuclear Cells (PBMC) of Healthy Volunteers

Project description:Intermittent hypoxia (IH) of obstructive sleep apnea (OSA) has been implicated in cardiovascular morbidity and mortality1. Although underlying mechanisms of the cardiovascular risk in OSA are not well defined, experiments in cell culture and animal models suggest that IH up-regulates pro-inflammatory genes that can promote atherosclerosis and insulin resistance. We hypothesized that short-term IH (5 h) will induce pro-inflammatory genes in healthy volunteers

2015-07-27 | GSE71356 | GEO

Serum proteomic analysis by tandem mass tags-based quantitative proteomics in pediatric obstructive sleep apnea

Project description:Pediatric obstructive sleep apnea (OSA) is a frequent respiratory disorder with an estimated prevalence of 3–6% in the general population. However, the underlying pathophysiology of OSA remains unclear. Recently, proteomic analysis using high-resolution and high-throughput mass spectrometry has been widely used in the field of medical sciences. In the present study, tandem mass tags (TMT)-based proteomic analysis was performed in the serum of patients with OSA.

2022-05-20 | PXD032734 | Pride

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