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| Status |
Public on Feb 02, 2015 |
| Title |
DNA Methylation Changes and Childhood Asthma in the Inner City [gene expression] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Background: Epigenetic marks, like asthma, are heritable. They are influenced by the environment, direct the maturation of T cellslymphocytes, and have been shown to enhance the development of allergic airways disease in mice. Thus, we hypothesized that epigenetic marks are associated with allergic asthma in inner-city children. Methods: We compared methylation patterns and gene expression in inner-city children with persistent atopic asthma versus healthy controls, using DNA and RNA from peripheral blood mononuclear cells (PBMCs) from inner city children aged 6-12 years with persistent atopic asthma children and healthy controls. Results were externally validated with the GABRIELA study population. Results: Comparing asthmatics (N=97) to controls (N=97), we identified 81 regions that were differentially methylated. Several immune genes were hypomethylated in asthmatics, including IL-13, RUNX3, and a number of specific genes relevant to natural killer cells (KIR2DL4, KIR2DL3, KIR3DL1, and KLRD1) and T cells lymphocytes (TIGIT). 14 differentially methylated regions (DMRs) were associated with the serum IgE concentration of IgE, including RUNX3. These results were internally and externally validated with a global methylation assessment using a different methodology in our inner-city cohort and an independent European cohort (GABRIELA). Hypo- and hypermethylated genes tended to be associated with increased and decreased gene expression, respectively (P<0.6x10-11 for asthma and ; P<0.01 for IgE). To further explore the relationship between methylation and gene expression, we created a matrix of genomic changes in methylation versus transcriptional changes (methyl eQTL) for asthma, and identified cis- and trans-regulated genes whose expression was related to asthma asthma-associated methylation marks.
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| Overall design |
peripheral blood mononuclear cells (PBMCs) from 97 atopic asthmatic and 97 nonatopic nonasthmatic children
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| Contributor(s) |
Yang IV, Pedersen BS, Liu A, Schwartz DA |
| Citation(s) |
25769910 |
| |
| Submission date |
Sep 10, 2012 |
| Last update date |
Jun 03, 2015 |
| Contact name |
David Schwartz |
| E-mail(s) |
DAVID.SCHWARTZ@ucdenver.edu
|
| Phone |
303-724-1783
|
| Organization name |
University of Colorado, Anschutz Medical Campus
|
| Department |
Medicine
|
| Street address |
Anschutz Medical Campus
|
| City |
Aurora |
| State/province |
CO |
| ZIP/Postal code |
80045 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL16025 |
NimbleGen Homo sapiens Expression Array [100718_HG18_opt_expr] |
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| Samples (194)
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| This SubSeries is part of SuperSeries: |
| GSE40736 |
DNA Methylation Changes and Childhood Asthma in the Inner City |
|
| Relations |
| BioProject |
PRJNA174785 |
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