The number of children diagnosed with asthma and allergies has risen tremendously in the last few decades, partly because of higher awareness. But the jury is still out on determining what exactly is driving this increase. Rapid changes in the environment and lifestyles factors may be to blame, yet much remains to be learned about the etiology of both these ailments. To further our understanding, scientists have been investigating the role of epigenetics to determine which biological mechanisms play a role in these conditions.
While asthma and allergies can develop at any age, they frequently begin in childhood. It’s believed that some babies are born genetically prone to certain sensitivities, and the environment in which they grow up in likely affects how and when an allergic disorder emerges or develops. In some cases, a child will grow out of one sensitivity but then develop another type later on. This situation is often referred to as the “allergic march”, and it is commonly associated with atopic dermatitis (eczema) and food allergy in infancy, followed by allergic rhinitis (hay fever) and asthma as the child grows older.
For years, doctors and researchers have been fascinated with the allergic march – from how it starts to its progression in patients. Several studies have sought to find ways to halt the march. Now, new research could be improving upon this by evaluating the association between DNA methylation age (DNAmAge) and epigenetic age acceleration with childhood asthma and allergies. The study, which is part of Project Viva, a groundbreaking longitudinal cohort of women and children, was conducted at Brigham and Women’s Hospital and recently published in The Journal of Allergy & Clinical Immunology.
“We know that the prevalence of allergies and asthma has been increasing over the past decade. The genome hasn’t changed, but some of the ways that the environment is interacting with our genomes may have,” said Dawn DeNeo, MD, MPH, senior author of the study. “We wanted to explore if these mechanisms can be captured or measured by examining the epigenome. If so, we may have a way of better understanding early susceptibility to asthma and allergies and what exposures may be influencing the emergence of disease.”
In previous articles, we have discussed how epigenetics helps explain the origins of allergic conditions, and how pollution and other environmental factors can trigger a person’s susceptibility to these disorders even before birth. It’s been found that aberrant DNA methylation levels tend to correlate with an allergic predisposition, which is why studying this mechanism could eventually lead to finding ways to overcome or at least reduce the symptoms of asthma and allergies.
In the current study, the investigators examined DNA from blood samples taken from the children participating in the large cohort at various time periods: birth, early childhood, and mid-childhood. DNA methylation levels were then recorded and DNAmAge calculated using the Horvath method.
Methylation signifies a chemical change to DNA that can either activate or repress gene expression without altering the underlying genetic code. DNA methylation naturally changes over time and has been used to determine epigenetic age. In some individuals, epigenetic age is accelerated. This phenomenon has been labeled as DNA methylation age or DNAmAge. Prior research has used DNAmAge to investigate adult diseases such as Parkinson’s and lung cancer, but it has not been used to analyze allergies or asthma in children. This study was the first to determine if DNAmAge and age acceleration are associated with allergic phenotypes.
The overall results indicated that by mid-childhood, advanced DNAmAge correlated to higher levels of IgE, which are antibodies found in the blood of allergic individuals, as well as increased risk for atopic sensitization, environmental and food allergies, and asthma. These findings were also then replicated in a similar Costa Rica cohort.
DeMeo and her team believe that this heightened epigenetic age stems from early life exposure, given that associations are being seen by mid-childhood. She stated, “There are likely environmental exposures and DNA changes that are occurring in this window of time that do not seem to be apparent at birth. If we can target our future investigations on early exposures such as nutrition, we may be able to use epigenetic clocks to find out what changes we can make to modify this trajectory toward the development of asthma and allergy.”
The relationship between DNAmAge’s and allergies/asthma is correlative, as the study points out. The data found here cannot conclude if epigenetic alterations are responsible for allergic conditions. As well, it should be noted that the calculations used to estimate epigenetic age were not optimized for juveniles, but rather adults. More research is needed to refine the researcher’s analysis. Their goal is to study similar cohorts using improved biochemical tests, or epigenetic clocks, that are designed specifically for children.
Source: Peng C et. al. (February 2019). Epigenetic age acceleration is associated with allergy and asthma in children in Project Viva. J Allergy Clin Immunol.
Reference: Brigham and Women’s Hospital. “Study Links Epigenetic Age with Childhood Allergy, Asthma: Ticking of DNA methylation clocks tied to higher odds of asthma and atopy in children,” Brigham and Women’s Hospital Press Release. April 2019.