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Forkhead Box P3 Methylation and Expression in Men with Obstructive Sleep Apnea

1
Translational Research Unit, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón (IISAragón), 50009 Zaragoza, Spain
2
Biochemical Genetics Laboratory (LAGENBIO), Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria 0de Aragón (IISAragón), University of Zaragoza, 50013 Zaragoza, Spain
3
Departamento de Anatomía Embriología y Genética Animal, Instituto Agroalimentario de Aragón (IA2), Universidad de Zaragoza, 50013 Zaragoza, Spain
4
Departamento de Patología Animal, Facultad de Veterinaria, Instituto Agroalimentario de Aragón (IA2), Universidad de Zaragoza, 50013 Zaragoza, Spain
5
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERes), 28000 Madrid, Spain
6
Department of Respiratory Medicine, Clínica Universidad de Navarra, 31008 Pamplona, Spain
7
Respiratory Service, Hospital Universitario Miguel Servet, University of Zaragoza, 50009 Zaragoza, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Dr Jose M. Marin and Dr. Inmaculada Martin-Burriel are both the senior authors of this collaborative work.
Int. J. Mol. Sci. 2020, 21(6), 2233; https://doi.org/10.3390/ijms21062233
Received: 22 January 2020 / Revised: 17 March 2020 / Accepted: 19 March 2020 / Published: 23 March 2020
(This article belongs to the Special Issue Genetic Markers in Sleep Disorders)
Background: Epigenetic changes in obstructive sleep apnea (OSA) have been proposed as a mechanism for end-organ vulnerability. In children with OSA, Forkhead Box P3 (FOXP3) DNA methylation were associated with inflammatory biomarkers; however, the methylation pattern and its effect in the expression of this gene have not been tested in adults with OSA. Methods: Plasma samples from subjects without comorbid conditions other than OSA were analyzed (the Epigenetics Status and Subclinical Atherosclerosis in Obstructive Sleep Apnea (EPIOSA) Study: NCT02131610). In 16 patients with severe OSA (Apnea-Hypopnea Index—AHI- > 30 events/h) and seven matched controls (AHI < 5), methylation of FOXP3 gen was evaluated by PCR of the promoter and by pyrosequencing of the intron 1 Treg-specific demethylated region (TSDR). In another 74 patients with OSA (AHI > 10) and 31 controls, we quantified FOXP3 protein expression by ELISA and gene expression by quantitative real-time PCR. C-reactive protein (CRP) and plasma Treg cells were also evaluated. Results: Neither the levels of the promoter nor the TSDR demethylated region were different between controls and patients with OSA, whether they were grouped by normal or high CRP. FOXP3 protein and mRNA expression did not differ between groups. Conclusions: FOXP3 methylation or its expression is not altered in adults with OSA, whatever their inflammatory status. View Full-Text
Keywords: obstructive sleep apnea; FOXP3 methylation; FOXP3 expression; epigenetics. obstructive sleep apnea; FOXP3 methylation; FOXP3 expression; epigenetics.
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MDPI and ACS Style

Sanz-Rubio, D.; Sanz, A.; Varona, L.; Bolea, R.; Forner, M.; Gil, A.V.; Cubero, P.; Marin-Oto, M.; Martin-Burriel, I.; Marin, J.M. Forkhead Box P3 Methylation and Expression in Men with Obstructive Sleep Apnea. Int. J. Mol. Sci. 2020, 21, 2233.

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