By Megan Brooks
NEW YORK (Reuters Health) - Researchers have identified DNA-methylation profiles in nasal epithelium that are associated with, and can accurately classify, atopy and atopic asthma in children.
"Our findings strongly suggest that abnormalities in the airway epithelium are critical to the development of atopic (allergic) asthma, which could have important implications for the prevention and management of this disease," said Dr. Juan Celedon of the University of Pittsburgh, Pennsylvania.
"Moreover, we show that measuring DNA methylation profiles in nasal epithelium accurately classifies children according to whether they have allergy or allergic asthma," he told Reuters Health by email.
Epigenetic mechanisms could alter the airway epithelial barrier leading to atopic diseases such as asthma, Dr. Celedon and colleagues note in The Lancet Respiratory Medicine, online December 21.
To their knowledge, theirs is the first genome-wide study of the nasal epithelium methylome and atopy, and the first such study of atopic asthma in a large sample of children.
Among 483 Puerto Rican children 9 to 20 years old, DNA-methylation profiles in nasal epithelium (a surrogate for bronchial epithelium) were "markedly" different between the 312 children with and the 171 children without atopy, they found.
After adjusting for covariates and multiple testing, they identified 8,664 CpG sites that were significantly associated with atopy and atopic asthma.
"These CpGs were in or near genes relevant to epithelial barrier function, including CDHR3 and CDH26, and in other genes related to airway epithelial integrity and immune regulation, such as FBXL7, NTRK1, and SLC9A3," the researchers report.
They replicated 28 of the top 30 CpGs in two independent cohorts from different ethnic backgrounds.
They also designed a 30-CpG panel that accurately classified children according to atopy, with an area under the curve (AUC) of 0.93 to 0.94 and an accuracy of 85% to 88% in the original cohort, and an AUC of 0.74 to 0.92 and an accuracy of 68% to 82% in both replication cohorts.
The CpG panel also performed well for atopic asthma (AUC, 0.95 to 1.00 in the original cohort, and 0.82 to 0.88 in the replication cohorts). "Our findings were robust to differences in ethnic and racial background, geographic location, and environmental exposures across cohorts," the researchers write.
They say nasal methylation profiles "could be used for early prediction of asthma, identifying early-life environmental risk factors for asthma and assessing response to asthma therapies in children."
"Because our study was cross-sectional, we cannot determine which methylation profiles linked to allergy or allergic asthma occurred before or after the disease began," Dr. Celedon told Reuters Health. "The next step is to conduct studies in newborns, to see whether measuring DNA methylation in nasal epithelium can predict the development of allergy and allergic asthma over time."
The study was funded by the National Institutes of Health. Dr. Celedon has no relevant disclosures.
Lancet Respir Med 2018.