DNA methylation profiling of blood monocytes in obesity hypoventilation syndrome patients: Effect of positive airway pressure treatment.

Cortese R, Zhang C, Bao R, Andrade J, Khalyfa A, Mokhlesi B, Gozal D. Chest. 2016 Feb 25.

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, as well as for obesity-hypoventilation syndrome (OHS), its most severe phenotype. However, the molecular and cellular mechanisms underlying OHS-induced morbidities and their response to PAP treatment remain unclear, and could be mediated, in part, by OSA-induced epigenetic changes.
METHODS: Blood was collected before starting PAP treatment (PRE- group), as well as 6 weeks after PAP treatment (POST-group) in 15 adult OHS patients. DNA methylation profiles were studied by methylated DNA immunoprecipitation coupled to microarrays (MeDIP-chip) in 6 representative patients and further verified in a cohort of 15 patients by MeDIP-qPCR. further verified in a cohort of 15 patients by MeDIP-qPCR RESULTS: 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 (PRE/POST Fold changes: ABCA1=3.11, ABCG1=1.72, CD36=5.04, FABP4=2.49, HMOX=2.74, NOS2=7.78, PEPCK1=9.27, and ADIPOQ=1.73), 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 OHS patients that are responsive to PAP treatment. We postulate that differentially methylated regions in blood monocytes may serve as potential biomarkers in clinical practice for monitoring the disease and the associated co-morbidities.

Ventana Cientifica. Mayo 2016. Artículo 151
DNA methylation profiling of blood monocytes in obesity hypoventilation syndrome patients: Effect of positive airway pressure treatment.