DNA methylation and childhood asthma in the inner city

• Published in: Journal of allergy and clinical immunology Vol. 136; no. 1; pp. 69 - 80
• Main Authors: Yang, Ivana V., Pedersen, Brent S., Liu, Andrew, O'Connor, George T., Teach, Stephen J., Kattan, Meyer, Misiak, Rana Tawil, Gruchalla, Rebecca, Steinbach, Suzanne F., Szefler, Stanley J., Gill, Michelle A., Calatroni, Agustin, David, Gloria, Hennessy, Corinne E., Davidson, Elizabeth J., Zhang, Weiming, Gergen, Peter, Togias, Alkis, Busse, William W., Schwartz, David A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2015; Elsevier Limited
• Subjects: Allergies; Allergy and Immunology; Asthma; Asthma - genetics; Asthma - immunology; atopic asthma; Child; Consortia; Core Binding Factor Alpha 3 Subunit - genetics; Data collection; Deoxyribonucleic acid; DNA; DNA - analysis; DNA Methylation; Epigenesis, Genetic; Epigenetics; Female; Gene expression; Humans; Immunoglobulin E - blood; inner city; Interleukin-1 Receptor-Like 1 Protein; Interleukin-13 - genetics; Interleukin-4 - genetics; Laboratories; Leukocytes, Mononuclear - physiology; Male; Population; Principal components analysis; Quality; Receptors, Cell Surface - genetics; Receptors, Immunologic - genetics; Respiratory Function Tests; RNA - analysis; Studies; TH2 immunity; Urban Population; atopic asthma; inner city; PC; WTA; TH2 immunity; PEER; DNA methylation; DMR; NK; RUNX3; epigenetics; PCA; T H2 immunity; Principal components analysis; Differentially methylated region; Runt-related transcription factor 3; Principal component; Whole transcriptome–amplified; Probabilistic estimation of expression residuals; Natural killer; T(H)2 immunity
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2015.01.025

Epigenetic marks are heritable, influenced by the environment, direct the maturation of T lymphocytes, and in mice enhance the development of allergic airway disease. Thus it is important to define epigenetic alterations in asthmatic populations. We hypothesize that epigenetic alterations in circulating PBMCs are associated with allergic asthma. We compared DNA methylation patterns and gene expression in inner-city children with persistent atopic asthma versus healthy control subjects by using DNA and RNA from PBMCs. Results were validated in an independent population of asthmatic patients. Comparing asthmatic patients (n = 97) with control subjects (n = 97), we identified 81 regions that were differentially methylated. Several immune genes were hypomethylated in asthma, including IL13, RUNX3, and specific genes relevant to T lymphocytes (TIGIT). Among asthmatic patients, 11 differentially methylated regions were associated with higher serum IgE concentrations, and 16 were associated with percent predicted FEV1. Hypomethylated and hypermethylated regions were associated with increased and decreased gene expression, respectively (P < 6 × 10−12 for asthma and P < .01 for IgE). We further explored the relationship between DNA methylation and gene expression using an integrative analysis and identified additional candidates relevant to asthma (IL4 and ST2). Methylation marks involved in T-cell maturation (RUNX3), TH2 immunity (IL4), and oxidative stress (catalase) were validated in an independent asthmatic cohort of children living in the inner city. Our results demonstrate that DNA methylation marks in specific gene loci are associated with asthma and suggest that epigenetic changes might play a role in establishing the immune phenotype associated with asthma.