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DNA methylation profiling in blood of OSA patients and controls

ABSTRACT: DNA methylation profiling in blood of OSA patients and controls

PROVIDER: PRJNA786638 | ENA |

REPOSITORIES: ENA

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DNA methylation profiling in blood of OSA patients and controls

Project description: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.

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DNA methylation profiling of blood monocytes in obstructive sleep apnea (OSA) patients: Effect of positive airway pressure (PAP) treatment.

Project description:Background: Obstructive sleep apnea (OSA) is a highly prevalent condition that is associated with a wide range of long-term morbidities including metabolic, cardiovascular, and cognitive alterations, possibly via activation of systemic inflammatory and oxidative stress pathways. Implementation of positive airway pressure (PAP) is the first line treatment for OSA. However, the molecular and cellular mechanisms underlying OSA-induced morbidities and their response to PAP treatment remain unclear. Methods And Results: DNA methylation profiles were examined in blood monocytes of OSA patients before and after PAP treatment. We identified 1,847 regions showing significant differential DNA methylation (p<0.001 and MAT score >4) between the groups. Analysis of biochemical pathways and gene networks demonstrated that differentially methylated regions (DMRs) were associated with immune responses, and particularly with mechanisms governing gene regulation by peroxisome proliferation-activated receptors (PPAR). Single locus quantitative PCR analysis revealed that DNA methylation was increased at the PPAR responsive elements (PPAREs) of 8 genes in the post-treatment samples, suggesting that PAP treatment leads to an increase in DNA methylation at PPAREs, possibly affecting the binding of the PPARG complex and downstream gene expression. Conclusions: Our work provides initial evidence of epigenetic regulation particularly involving metabolic pathways in OSA patients that are responsive to PAP treatment. We postulate that differentially methylated regions in blood monocytes may serve as potential biomarkers in clinical practice.

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