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Epigenetics. 2014 Jul;9(7):998-1006. doi: 10.4161/epi.28945. Epub 2014 Apr 24.

Epigenome-wide association study reveals longitudinally stable DNA methylation differences in CD4+ T cells from children with IgE-mediated food allergy.

Author information

1
Murdoch Childrens Research Institute; Royal Children's Hospital; Melbourne, VIC Australia; NHMRC Centre for Food and Allergy Research; Murdoch Childrens Research Institute; Royal Children's Hospital; Melbourne, VIC Australia; Honorary Fellow University of Melbourne; Melbourne, VIC Australia.
2
Murdoch Childrens Research Institute; Royal Children's Hospital; Melbourne, VIC Australia.
3
Murdoch Childrens Research Institute; Royal Children's Hospital; Melbourne, VIC Australia; NHMRC Centre for Food and Allergy Research; Murdoch Childrens Research Institute; Royal Children's Hospital; Melbourne, VIC Australia.
4
Childhood Allergy and Immunology Research; School of Paediatrics and Child Health; University of Western Australia; Crawley, WA Australia.

Erratum in

Abstract

Food allergy is mediated by a combination of genetic and environmental risk factors, potentially mediated by epigenetic mechanisms. CD4+ T-cells are key drivers of the allergic response, and may therefore harbor epigenetic variation in association with the disease phenotype. Here we retrospectively examined genome-wide DNA methylation profiles (~450,000 CpGs) from CD4+ T-cells on a birth cohort of 12 children with IgE-mediated food allergy diagnosed at 12-months, and 12 non-allergic controls. DNA samples were available at two time points, birth and 12-months.

CASE:

control comparisons of CD4+ methylation profiles identified 179 differentially methylated probes (DMP) at 12-months and 136 DMP at birth (FDR-adjusted P value<0.05, delta β>0.1). Approximately 30% of DMPs were coincident with previously annotated SNPs. A total of 92 [corrected] allergy-associated non-SNP DMPs were present at birth when individuals were initially disease-free, potentially implicating these loci in the causal pathway. Pathway analysis of differentially methylated genes identified several MAP kinase signaling molecules. Mass spectrometry was used to validate 15 CpG sites at 3 candidate genes. Combined analysis of differential methylation with gene expression profiles revealed gene expression differences at some but not all allergy associated differentially methylated genes. Thus, dysregulation of DNA methylation at MAPK signaling-associated genes during early CD4+ T-cell development may contribute to suboptimal T-lymphocyte responses in early childhood associated with the development of food allergy.

KEYWORDS:

EWAS; Infinium 450k; allergic disease; food allergy; in utero programming; metastable epialleles

PMID:
24762976
PMCID:
PMC4143415
DOI:
10.4161/epi.28945
[Indexed for MEDLINE]
Free PMC Article
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