DNA methylation and childhood asthma in the inner city

Ivana V. Yang, Brent S. Pedersen, Andrew Liu, George T. O'Connor, Stephen J. Teach, Meyer Kattan, Rana Tawil Misiak, Rebecca Gruchalla, Suzanne F. Steinbach, Stanley J. Szefler, Michelle A. Gill, Agustin Calatroni, Gloria David, Corinne E. Hennessy, Elizabeth J. Davidson, Weiming Zhang, Peter Gergen, Alkis Togias, William W. Busse, David A. Schwartz

Research output: Contribution to journalArticle

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Abstract

Background: 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. Objective: We hypothesize that epigenetic alterations in circulating PBMCs are associated with allergic asthma. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
JournalJournal of Allergy and Clinical Immunology
DOIs
StateAccepted/In press - Jun 2 2014

Fingerprint

DNA Methylation
Asthma
Epigenomics
T-Lymphocytes
Gene Expression
Interleukin-4
Immunoglobulin E
Genes
Interleukin-13
Catalase
Methylation
Population
Immunity
Healthy Volunteers
Oxidative Stress
RNA
Phenotype
DNA
Serum

Keywords

  • Atopic asthma
  • DNA methylation
  • Epigenetics
  • Inner city
  • T2 immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Yang, I. V., Pedersen, B. S., Liu, A., O'Connor, G. T., Teach, S. J., Kattan, M., ... Schwartz, D. A. (Accepted/In press). DNA methylation and childhood asthma in the inner city. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2015.01.025

DNA methylation and childhood asthma in the inner city. / 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.

In: Journal of Allergy and Clinical Immunology, 02.06.2014.

Research output: Contribution to journalArticle

Yang, IV, Pedersen, BS, Liu, A, O'Connor, GT, Teach, SJ, Kattan, M, Misiak, RT, Gruchalla, R, Steinbach, SF, Szefler, SJ, Gill, MA, Calatroni, A, David, G, Hennessy, CE, Davidson, EJ, Zhang, W, Gergen, P, Togias, A, Busse, WW & Schwartz, DA 2014, 'DNA methylation and childhood asthma in the inner city', Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2015.01.025
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. / DNA methylation and childhood asthma in the inner city. In: Journal of Allergy and Clinical Immunology. 2014.
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AU - Yang, Ivana V.

AU - Pedersen, Brent S.

AU - Liu, Andrew

AU - O'Connor, George T.

AU - Teach, Stephen J.

AU - Kattan, Meyer

AU - Misiak, Rana Tawil

AU - Gruchalla, Rebecca

AU - Steinbach, Suzanne F.

AU - Szefler, Stanley J.

AU - Gill, Michelle A.

AU - Calatroni, Agustin

AU - David, Gloria

AU - Hennessy, Corinne E.

AU - Davidson, Elizabeth J.

AU - Zhang, Weiming

AU - Gergen, Peter

AU - Togias, Alkis

AU - Busse, William W.

AU - Schwartz, David A.

PY - 2014/6/2

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N2 - Background: 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. Objective: We hypothesize that epigenetic alterations in circulating PBMCs are associated with allergic asthma. Methods: 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. Results: 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. Conclusions: 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.

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KW - Atopic asthma

KW - DNA methylation

KW - Epigenetics

KW - Inner city

KW - T2 immunity

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