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The nasal methylome and childhood atopic asthma.

ABSTRACT: BACKGROUND:Given the strong environmental influence on both epigenetic marks and allergic asthma in children, the epigenetic alterations in respiratory epithelia might provide insight into allergic asthma. OBJECTIVE:We sought 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 control subjects (n = 36). Results were validated in an independent population of asthmatic children (n = 30) by using a shared healthy control population (n = 36) and in an independent population of white adult atopic asthmatic patients (n = 12) and control subjects (n = 12). RESULTS:We identified 186 genes with significant methylation changes, differentially methylated regions or differentially methylated probes, after adjustment for age, sex, race/ethnicity, batch effects, inflation, and multiple comparisons. Genes differentially methylated included those with established roles in asthma and atopy and genes related to extracellular matrix, immunity, cell adhesion, epigenetic regulation, and airflow obstruction. The methylation changes were substantial (median, 9.5%; range, 2.6% to 29.5%). Hypomethylated and hypermethylated genes were associated with increased and decreased gene expression, respectively (P < 2.8 × 10-6 for differentially methylated regions and P < 7.8 × 10-10 for differentially methylated probes). Quantitative analysis in 53 differentially expressed genes demonstrated that 32 (60%) have significant methylation-expression relationships within 5 kb of the gene. Ten 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. Sixty-seven of 186 genes also have significant asthma-associated methylation changes in nasal epithelia of adult white asthmatic patients. CONCLUSIONS:Epigenetic marks in respiratory epithelia are associated with allergic asthma and gene expression changes in inner-city children.

SUBMITTER: Yang IV

PROVIDER: S-EPMC5391298 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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The nasal methylome and childhood atopic asthma.

Yang Ivana V IV Pedersen Brent S BS Liu Andrew H AH O'Connor George T GT Pillai Dinesh D Kattan Meyer M Misiak Rana Tawil RT Gruchalla Rebecca R Szefler Stanley J SJ Khurana Hershey Gurjit K GK Kercsmar Carolyn C Richards Adam A Stevens Allen D AD Kolakowski Christena A CA Makhija Melanie M Sorkness Christine A CA Krouse Rebecca Z RZ Visness Cynthia C Davidson Elizabeth J EJ Hennessy Corinne E CE Martin Richard J RJ Togias Alkis A Busse William W WW Schwartz David A DA

The Journal of allergy and clinical immunology 20161013 5

<h4>Background</h4>Given the strong environmental influence on both epigenetic marks and allergic asthma in children, the epigenetic alterations in respiratory epithelia might provide insight into allergic asthma.<h4>Objective</h4>We sought to identify DNA methylation and gene expression changes associated with childhood allergic persistent asthma.<h4>Methods</h4>We compared genomic DNA methylation patterns and gene expression in African American children with persistent atopic asthma (n = 36) v ...[more]

PMID: 27745942

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Project description:Background: Nasal epithelia are emerging as a proxy measure of gene expression of the airway epithelium in asthma. We hypothesized that epigenetic marks regulate gene expression of the nasal epithelia and consequently may provide a novel target for allergic 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 asthmatics [N=30]. Results: We identified 186 genes with significant methylation changes, either as regions (differentially methylated regions [DMRs]) or single CpGs (differentially methylated probes [DMPs]) after adjustment for age, gender, race/ethnicity, batch effects, inflation, and multiple comparisons (false discovery rate-adjusted q<0.05). Genes differentially methylated include those with established roles in asthma and atopy, components of the extracellular matrix, genes related to immunity, cell adhesion, epigenetic regulation, and airway obstruction. The methylation changes are large (median 9.5%, range: 2.6-29.5% methylation change) and similar in magnitude to those observed in malignancies. 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 of methylation-expression relationships in 53 differentially expressed genes demonstrated that 32 (60%) have significant (q<0.05) methylation-expression relationships within 5kb of the gene. 10 loci selected based on the relevance to asthma, magnitude of methylation change, and asthma specific methylation-expression relationships were validated in an independent cohort of children with asthma. Conclusions: Our findings that epigenetic marks in respiratory epithelia are associated with allergic asthma in inner-city children provide new targets for biomarker development, and novel approaches to understanding disease pathogenesis. case control design with nasal epithelial cells from 36 atopic asthmatic and 36 nonatopic nonasthmatic children from the inner city

Dataset Information

The nasal methylome and childhood atopic asthma.

Publications

The nasal methylome and childhood atopic asthma.

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