Epigenetics of obstructive sleep apnea syndrome: a systematic review

Abstract

Study objectives: Obstructive sleep apnea (OSA) is a chronic and widely prevalent disease associated with multiple health disorders. Current diagnostic strategies for OSA are limited because of cost, time, and access. Epigenetic signatures offer insight into the relationships between disease and environment and could play a significant role in developing both diagnostic and therapeutic tools for OSA. In the current study, a systematic literature search was conducted to investigate the existing evidence of OSA-associated epigenetic modifications.

Methods: A systematic literature search was performed using electronic academic databases including PubMed, CINAHL, Scopus, Embase, EBM Reviews, and Web of Science. However, the current study focused on screening for original, English-language articles pertaining to OSA and associated epigenetic mechanisms. To produce unbiased results, screening was performed independently by authors.

Results: We identified 2,944 publications in our systematic search. Among them, 65 research articles were related to OS A-associated differential gene expression, genetic variation, and epigenetic modifications. Although these 65 articles were considered for full manuscript review, only 12 articles met the criteria of OSA-associated epigenetic modifications in human and animal models. Human patients with OSA had unique epigenetic changes compared to healthy control patients and, interestingly, epigenetic signatures were commonly identified in genes associated with metabolic and inflammatory pathways.

Conclusions: Although the available studies are limited, this research provides novel insights for the development of epigenetic markers for the diagnosis and treatment of OSA. Thorough genome-wide investigations will be required to develop cost-effective, robust biomarkers for the identification of OSA among children and adults. Here, we offer a study design for such efforts.

Citation: Leader BA, Koritala BSC, Moore CA, Dean EG, Kottyan LC, Smith DF. Epigenetics of obstructive sleep apnea syndrome: a systematic review. J Clin Sleep Med. 2021;17(12):2533-2541.

Keywords: biomarkers; epigenetics; obstructive sleep apnea; systematic review.

Figure 1. PRISMA diagram of systematic review for epigenetics and obstructive sleep apnea.

Overview of the number of studies that were included or excluded in each phase of the study selection procedure, as outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. OSA = obstructive sleep apnea.

Figure 2. A prospective study design for the development of OSA-specific epigenetic biomarkers.

To develop OSA-specific epigenetic biomarkers, DNA, RNA, or proteins should be purified from tissue samples of both healthy patients and patients with OSA. The listed epigenetic methods may be used for understanding the OSA-specific epigenetic signatures. ChIP = chromatin immunoprecipitation, ELISA = enzyme-linked immunosorbent assay, HITS = high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation, OSA = obstructive sleep apnea, PCR = polymerase chain reaction.