Abstract
DNA methylation changes may predispose becoming IgE-sensitized to allergens. We analyzed whether DNA methylation in peripheral blood mononuclear cells (PBMC) is associated with IgE sensitization at 5 years of age (5Y). DNA methylation was measured in 288 PBMC samples from 74 mother/child pairs from the birth cohort ALADDIN (Assessment of Lifestyle and Allergic Disease During INfancy) using the HumanMethylation450BeadChip (Illumina). PBMCs were obtained from the mothers during pregnancy and from their children in cord blood, at 2 years and 5Y. DNA methylation levels at each time point were compared between children with and without IgE sensitization to allergens at 5Y. For replication, CpG sites associated with IgE sensitization in ALADDIN were evaluated in whole blood DNA of 256 children, 4 years old, from the BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology) cohort. We found 34 differentially methylated regions (DMRs) associated with IgE sensitization to airborne allergens and 38 DMRs associated with sensitization to food allergens in children at 5Y (Sidak p ≤ 0.05). Genes associated with airborne sensitization were enriched in the pathway of endocytosis, while genes associated with food sensitization were enriched in focal adhesion, the bacterial invasion of epithelial cells, and leukocyte migration. Furthermore, 25 DMRs in maternal PBMCs were associated with IgE sensitization to airborne allergens in their children at 5Y, which were functionally annotated to the mTOR (mammalian Target of Rapamycin) signaling pathway. This study supports that DNA methylation is associated with IgE sensitization early in life and revealed new candidate genes for atopy. Moreover, our study provides evidence that maternal DNA methylation levels are associated with IgE sensitization in the child supporting early in utero effects on atopy predisposition.
Highlights
During the last decades, the prevalence of allergic sensitization and allergic diseases has increased worldwide
The final dataset considered for DNA methylation analysis included a total of 270 peripheral blood mononuclear cells (PBMC) samples from the mothers obtained during pregnancy (n = 71), from cord blood (CB, n = 64), and the child at
The3 of final dataset considered for DNA methylation analysis included a total of 270 PBMC samples from the mothers obtained during pregnancy (n = 71), from cord blood (CB, n = 64), and the child at 2 years (2Y) (n = 64), and 5 years (5Y) (n = 71) (Figure 1)
Summary
The prevalence of allergic sensitization and allergic diseases has increased worldwide. DNA methylation is of interest because it is very dynamic in several immune genes early in life [3]. IgE sensitization to food and airborne allergens usually starts during early childhood and is for many children the first step in the progression to clinical manifestations such as atopic eczema, food allergy, seasonal or perennial rhinitis, and/or asthma [4]. Some studies have evaluated the association between DNA methylation and the development of allergen-specific IgE sensitization [5,6,7,8,9]. The cross-sectional design of these studies imposes the limitation that it is not possible to know if the observed
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