PURPOSE OF THE STUDY.
To determine if epigenetic changes play a role in asthma phenotypes.
There were 2 groups studied, both involved children enrolled from pregnancy cohorts. The first group (Menorca cohort) was 122 children with data available through age 6 years. The second group (Sabadell cohort) was 236 children with available DNA extracted from whole cord blood.
Children were assigned wheezing phenotypes at age 4 to 6 years based on validated questionnaires (never, transient, late-onset, or persistent wheezing). Prenatal exposure data were collected through questionnaire and by measuring for presence of a specific pollutant, dichlorodiphenyldichloroethylene, in cord blood.
DNA hypomethylation was associated with increased risk for persistent wheezing in both studies, although only 1 of the 2 was statistically significant (Menorca: odds ratio 1.13, 95% confidence interval 0.99–1.29, P = .077; Sabadell: odds ratio 1.16, 95% confidence interval 1.03–1.37, P = .017). Higher levels of dichlorodiphenyldichloroethylene were associated with hypomethylation of ALOX12 in the Menorca study (P = .033), but not the Sabadell study (P = .377). Level of methylation at ALOX12 was strongly influenced by polymorphisms in the gene.
DNA hypomethylation at ALOX12 was associated with a higher risk of persistent wheezing. This may be an epigenetic biomarker that predicts increased likelihood of persistent wheezing in childhood.
This study adds to the knowledge that genes and the environment combine to influence asthma phenotype. In this case, ALOX12, a gene associated with airway inflammation, appears to exhibit variation in methylation, not based on genotype alone, but possibly on environmental factors, including prenatal pollutant exposure. Therefore, the degree of methylation at certain CpG sites on this gene may be an early biomarker that helps to predict wheezing phenotype.
- Copyright © 2012 by the American Academy of Pediatrics