DNA methylation and childhood asthma in the inner city

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:136

Article

Yang, Ivana V.^1,2,3  Pedersen, Brent S.¹  Liu, Andrew^2,3  O'Connor, George T.⁴  Teach, Stephen J.⁵  Kattan, Meyer⁶  Misiak, Rana Tawil⁷  Gruchalla, Rebecca⁸  Steinbach, Suzanne F.⁴  Szefler, Stanley J.^9,10  Gill, Michelle A.⁸  Calatroni, Agustin¹¹  David, Gloria¹¹  Hennessy, Corinne E.¹  Davidson, Elizabeth J.¹  Zhang, Weiming¹²  Gergen, Peter¹⁴  Togias, Alkis¹⁴  Busse, William W.¹⁵  Schwartz, David A.^1,2,3,13 

[1] Univ Colorado, Sch Med, Dept Med, Aurora, CO 80045 USA

[2] Natl Jewish Hlth, Dept Pediat, Denver, CO USA

[3] Natl Jewish Hlth, Dept Med, Denver, CO USA

[4] Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA

[5] Childrens Natl Hlth Syst, Washington, DC USA

[6] Columbia Univ, Med Ctr, New York, NY USA

[7] Henry Ford Hosp, Dept Med, Detroit, MI 48202 USA

[8] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA

[9] Childrens Hosp Colorado, Dept Pediat, Colorado Springs, CO USA

[10] Univ Colorado, Sch Med, Aurora, CO 80045 USA

[11] Rho Fed Syst Div, Chapel Hill, NC USA

[12] Univ Colorado, Colorado Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO 80045 USA

[13] Univ Colorado, Dept Immunol, Aurora, CO 80045 USA

[14] NIAID, Bethesda, MD 20892 USA

[15] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI USA

关键词: DNA methylation;    atopic asthma;    epigenetics;    T(H)2 immunity;    inner city;   

DOI  :  10.1016/j.jaci.2015.01.025

来源: Elsevier

【 摘 要 】

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 x 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), T(H)2 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.

【 授权许可】

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