Background
Given strong environmental influence on both epigenetic marks and allergic asthma in children, the epigenetic alterations in respiratory epithelia may provide insight into allergic asthma.
Objective
To identify DNA methylation and gene expression changes associated with childhood allergic persistent asthma.
Methods
We compared genomic DNA methylation patterns and gene expression in African American children with persistent atopic asthma[N=36] versus healthy controls[N=36]. Results were validated in an independent population of asthmatic children[N=30] using a shared healthy control population[N=36] and in independent population of Caucasian adult atopic asthmatics[N=12] and controls[N=12].
Results
We identified 186 genes with significant methylation changes, differentially methylated regions(DMRs) or differentially methylated probes(DMPs), after adjustment for age, gender, race/ethnicity, batch effects, inflation, and multiple comparisons. Genes differentially methylated included those with established roles in asthma and atopy, genes related to extracellular matrix, immunity, cell adhesion, epigenetic regulation, and airflow obstruction. The methylation changes were substantial (median 9.5%, range:2.6–29.5%). Hypo- and hyper-methylated genes were associated with increased and decreased gene expression respectively (P<2.8x10−6 for DMRs and P<7.8x10−10 for DMPs). Quantitative analysis in 53 differentially expressed genes demonstrated that 32(60%) have significant methylation-expression relationships within 5kb of the gene. 10 loci selected based on the relevance to asthma, magnitude of methylation change, and methylation-expression relationships were validated in an independent cohort of children with atopic asthma. 67/186 genes also have significant asthma-associated methylation changes in nasal epithelia of adult Caucasian asthmatics.
Conclusions
Epigenetic marks in respiratory epithelia are associated with allergic asthma and gene expression changes in inner-city children.