Research Increases on the Role of Epigenetics in OSA


In 2018, when the study of potentially modifiable genetic markers for sleep apnea was emerging, a group of researchers from Mexico published a study titled, “ Dad’s snoring may have left molecular scars in your DNA: The emerging role of epigenetics in sleep disorders.” 

That title seems to summarize succinctly the role epigenetics may play in sleep disorders, most notably obstructive sleep apnea (OSA).

Definition of Epigenetics

Epigenetics is the study of heritable phenotypic changes that do not alter the DNA sequence, which means that these changes may also be reversible. These changes can include histone modifications, noncoding RNAs, and DNA methylation. As the researchers in Mexico reported in 2018, epigenetics involves the relationship between environmental factors and gene expression.

“Environmental factors play an integral role in the way genes can be expressed,” Emily Cheung, a PhD candidate in biomedical engineering and researcher in epigenetics and pediatric sleep apnea at The George Washington University in Washington, DC, told Medscape Medical News. “Epigenetics is a mechanism that can regulate gene expression without changes to DNA base pair sequences.”

“This is an area of growing interest, with work being done across the globe to better understand the interplay between epigenetics and obstructive sleep apnea,” said Anita Shelgikar, MD, a professor of neurology at the University of Michigan Medical School in Ann Arbor, Michigan, and a spokesperson for the American Academy of Sleep Medicine, regarding epigenetics. “The emerging evidence holds promise that one day we may adapt our clinical practice to incorporate our understanding of the relationship between epigenetics and obstructive sleep apnea.”

Research into the role of epigenetics in OSA has focused on four areas, Shelgikar said: How epigenetic factors may influence adverse outcomes in OSA, how untreated OSA may influence epigenetic factors, if treatment of OSA can alter epigenetic factors, and if modification of epigenetic factors can affect OSA severity and treatment response or both.

Search for New OSA Biomarkers

The emphasis on epigenetics has given rise to research into biomarkers of OSA and sleep disorders. At his laboratory at the University of Missouri in Columbia, Missouri, Rene Cortese, PhD, an assistant professor of pediatrics and obstetrics, gynecology and women’s health, is researching how intermittent hypoxia and sleep fragmentation from OSA accelerates the aging process of blood vessel cells. That process, known as epigenetic age acceleration, is a marker of biological aging and has been linked to OSA and related comorbidities, Cortese said in an interview.

The need for new biomarkers that can help identify OSA early in the disease process is pressing because earlier intervention can prevent the onset of OSA and the multiple comorbidities such as cardiovascular disease (CVD), Cortese said. “Probably the most we know about all these metrics is the apnea-hypopnea index,” Cortese said. “We need to have something more.”

The role of hypoxia-mediated epigenetic regulation in cancer, pulmonary hypertension, adaptation to high altitudes, and cardiorenal disease has drawn much attention, he added.

Cortese recently received a $3 million National Institutes of Health grant to investigate the effect OSA has on cells in the vascular lining and potential treatments. The work will use mice to evaluate how epigenetic age acceleration causes the vascular cells to stop replicating. The thinking is that these cells can continue to release chemicals that trigger inflammation and vascular dysregulation, leading to CVD.

His work is targeting the p16 protein, which slows cell division. “Through the selective elimination of these cells, we believe we can tackle not just the negative impacts of OSA but maybe other aging-associate diseases,” Cortese said.

Cortese isn’t alone in his research into the role of epigenetics in sleep disorders. Cheung and her colleagues at The George Washington University have studied epigenetics in OSA in children. “Pediatric OSA increases the risk of cardiovascular, metabolic, and endothelial disease susceptibility in adulthood, specifically diseases such as obesity, hypertension, diabetes, and heart failure,” Cheung said.

Their research has focused on modifications to the epigenome and identified a microRNA, miR-92a, as a potential biomarker for childhood OSA. Researchers at the University of San Diego, San Diego, also reported on elevated miR-92a levels in children and adults with OSA.

In a preclinical study published last year, Cheung and her colleagues demonstrated that neonatal chronic intermittent hypoxia (CIH) exposure, a hallmark of OSA, resulted in an upregulation of genes in men, which they linked to inhibition of growth and nutrient utilization pathways, and a downregulation of genes in women, which they associated with increased cardiac inflammation.

Research has also focused on microRNA in OSA related to CVD. Researchers in China in 2023 reported that endothelial dysfunction is an early biomarker of CVD in adults and pediatric patients with CVD and that studies have shown that endothelial dysfunction in CIH is related to nitric oxide impairment, oxidative stress, and inflammation.

What Future Research Is Needed

But research into the relationship between epigenetics and OSA has a lot of gaps to fill, Cheung noted. “One of the first steps toward better understanding the long-term effects of epigenetic regulation in pediatric OSA is to perform prospective cohort studies, both clinical and preclinical, that track epigenetic changes from childhood into adulthood,” Cheung said.

Such research will provide insights into potentially modifiable epigenetic signatures and allow researchers to refine the list of epigenetic biomarkers that persist into adulthood, she said.

“Another direction of the field will be to understand the acute vs chronic effects of epigenetic modifications and how they influence a child’s cognitive and behavioral development,” Cheung added. “Finally, epigenetic signatures have the potential to be used as biomarkers to diagnose OSA and may become instrumental in future diagnostic panels that will assess a child’s predisposition of OSA, for early detection and treatment.” 

“It is a very new field,” Cortese told Medscape Medical News. “People are starting to recognize the potential of epigenetics, but it is a lot of work and we are at the very beginning.”

Cheung, Shelgikar, and Cortese had no relevant disclosures.

Richard Mark Kirkner is a medical journalist based in the Philadelphia area.



Source link : https://www.medscape.com/viewarticle/research-increases-role-epigenetics-osa-2024a1000jra?src=rss

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Publish date : 2024-10-29 13:21:46

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