Epigenetics dysfunction in morbid obesity with or without obstructive sleep apnoea: the EPIMOOSA study

Javier Lázaro, Paloma Clavería, Carmen Cabrejas, José Fernando, Berta Daga, Beatriz Ordoñez, Silvia Segura, David Sanz-Rubio, José M Marín, Javier Lázaro, Paloma Clavería, Carmen Cabrejas, José Fernando, Berta Daga, Beatriz Ordoñez, Silvia Segura, David Sanz-Rubio, José M Marín

Abstract

Background: Obstructive sleep apnoea (OSA) and morbid obesity (MO), defined by a body mass index ≥35 kg/m2, are two closely related conditions. Recent studies suggest that circulating microRNA (miRNA) plays a potential role in the physiopathology of both conditions. To date, circulating miRNA expression has been studied separately in both conditions, but never jointly. The primary treatment of OSA is continuous positive airway pressure (CPAP), whereas bariatric surgery (BS) is the treatment of choice for MO. We have thus initiated the Epigenetics modification in Morbid Obesity and Obstructive Sleep Apnoea (EPIMOOSA) study (ClinicalTrials.gov identifier: NCT03995836).

Methods/design: EPIMOOSA is a prospective non-interventional cohort study aiming to recruit 45 MO patients who are candidates for BS. Three groups will be formed: MO without OSA, MO with OSA without CPAP and MO with OSA and CPAP. All of them will be followed up in 4 visits: baseline, 6 months prior to BS and 3, 6 and 12 months post-BS. At baseline, OSA status will be assessed by home sleep polygraphy (HSP), and CPAP will be adopted according to national guidelines. A specific standardized questionnaire (including medical conditions and AOS-related symptoms) and anthropometrical examination will be performed at each visit. Blood samples will be obtained at each visit for immediate standard biochemistry, haematology and inflammatory cytokines. For bio-banking, serum, plasma, and circulating exosomes will also be obtained. Twenty-four hours of blood pressure and electrocardiogram (ECG) Holter monitoring will be performed at all visits. A new HSP will be performed at the last visit. Finally, the three groups will be sex- and age- matched with participants in the EPIOSA study, an ongoing study aimed at understanding epigenetic changes in non-obese OSA patients.

Discussion: EPIMOOSA will evaluate changes in circulating miRNA in MO with or without OSA for the first time. In addition, EPIMOOSA will be able to elucidate the influence of OSA in MO patients and how specific and combined treatments alter miRNA expression.

Keywords: Bariatric surgery; Continuous positive airway pressure; Epigenetics; Exosomes; Morbid obesity; Obstructive sleep apnoea.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Hypothetical relationship between chronic tissue hypoxia due to obesity and chronic intermittent hypoxia die to obstructive sleep apnoea and the overlap effect on the overexpression of miRNA in circulating exosomes
Fig. 2
Fig. 2
Time – line Follow up. HSP: home sleep polygraphy; OSA: Obstructive Sleep Apnoea; CPAP: Continous Positive Airway Pressure

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