By Matt Wood
Hearing a young child snore like Grandpa may be cute, but it’s not something to ignore. Excessive snoring in children is a symptom of obstructive sleep apnea (OSA), a condition marked by repeated episodes of obstructed breathing during sleep that has been linked to cognitive problems, obesity and long-term damage to the cardiovascular and metabolic systems.
In a new study, David Gozal, MD, chairman and professor of pediatrics at the University of Chicago Medicine, and his colleagues at the University of Chicago Section of Pediatric Sleep Medicine found that OSA is imprinted at an even deeper level in the body, in genes that help control the body’s immune system response.
As a leading expert on OSA, Gozal has long studied the detrimental effects of poor and fragmented sleep on children. His work has culminated in a number of studies with children that found that OSA can reduce a child’s IQ by as many as 10 points and increases the risk of childhood obesity.
In a recent lecture reviewing his ongoing pediatric sleep-medicine research, Gozal spoke about why he started studying sleep problems in children. “The major reason that I started all this work 15 years ago was because for many years, snoring and sleep apnea in children had been associated with behavioral problems such as hyperactivity, aggressiveness, problems with attention and learning problems,” he said.
In this latest study, published in the American Journal of Respiratory and Critical Care Medicine, the researchers looked in children with sleep apnea for changes in DNA methylation, one of the indicators of epigenetic changes. Epigenetics has gained attention in the past few years as a possible explanation for why patients vary in their response to diseases like cancer, metabolic and inflammatory diseases. Methylation is a process by which methyl groups or molecules attach to DNA and alter the expression of certain genes, essentially turning them off. Epigenetic modifications like DNA methylation, however, do not change the primary DNA sequence.
Sleep apnea puts a cumulative burden on the body that is made worse by the stress of decreased oxygen levels and increased sleep disruption. But children with sleep apnea have differing levels of their immune response, or systemic inflammation, so Gozal and his team hypothesized that epigenetic modifications could be responsible.
The study looked at DNA from children 5 to 10 years old with sleep apnea and found that it displayed increased methylation in the Forkhead box P3 gene (FOXP3), which plays a role in keeping a tight lid on immune system responses. The FOXP3 gene is involved in a process that controls the expression of proteins in regulatory T cells that suppress immune system responses. If the FOXP3 gene is highly methylated, or turned off, it limits the ability of these T cells to throttle the body’s immune system. It essentially stays in constant overdrive, putting stress on the body’s organs.
Among the children studied with sleep apnea, the researchers measured levels of high-sensitivity C-reactive protein (hsCRP), which rises in response to higher levels of inflammation. Children with both OSA and high levels of hsCRP displayed higher methylation of the FOXP3 gene than children with OSA and low levels of inflammation. Methylation levels also were higher in children with more severe symptoms of sleep apnea, suggesting that it might be an important biomarker for identifying children who are most at risk for long-term damage from OSA.
OSA is typically treated by procedures designed to keep the airway open so that breathing is not interrupted during sleep, such as a machine that delivers slightly pressurized air through a face mask to keep the windpipe open, dental devices and even surgery. Gozal said that while the findings from this study don’t suggest treatments by directly addressing increased DNA methylation, there are other potential options for treatment. “Interventions such as dietary modifications, antioxidants, and physical activity may have an effect that merits exploration,” he said.
In his talk, Gozal emphasized the importance of treating this condition as a chronic, low-grade, systemic inflammatory disease with serious risks for end-organ damage, and pointed out its surprising prevalence. “If you use the current criteria as defined by our profession for obstructive sleep apnea, 2 to 3 percent of all children 2 to 8 years of age will have sleep apnea. It’s a very prevalent disease, not one that we can ignore and pretend that does not exist,” he said.
Kim J, Bhattacharjee R, Khalyfa A, Kheirandish-Gozal L, Capdevila OS, Wang Y, & Gozal D (2012). DNA Methylation in Inflammatory Genes among Children with Obstructive Sleep Apnea. American journal of respiratory and critical care medicine, 185 (3), 330-8 PMID: 22077067