Acevedo, N.* ; Scala, G.* ; Merid, S.K.* ; Frumento, P.* ; Bruhn, S.* ; Andersson, A.* ; Ogris, C. ; Bottai, M.* ; Pershagen, G.* ; Koppelman, G.H.* ; Melén, E.* ; Sonnhammer, E.* ; Alm, J.* ; Söderhäll, C.* ; Kere, J.* ; Greco, D.* ; Scheynius, A.*
     
    
        
DNA methylation levels in mononuclear leukocytes from the mother and her child are associated with ige sensitization to allergens in early life.
    
    
        
    
    
        
        Int. J. Mol. Sci. 22:801 (2021)
    
    
    
      
      
	
	    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.
	
	
	    
	
       
      
	
	    
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        Publication type
        Article: Journal article
    
 
    
        Document type
        Scientific Article
    
 
    
        Thesis type
        
    
 
    
        Editors
        
    
    
        Keywords
        Alladin ; Allergens ; Atopy ; Bamse ; Dna Methylation ; Epigenetics ; Ige Sensitization ; Maternal Effects
    
 
    
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        Language
        english
    
 
    
        Publication Year
        2021
    
 
    
        Prepublished in Year
        
    
 
    
        HGF-reported in Year
        2021
    
 
    
    
        ISSN (print) / ISBN
        1661-6596
    
 
    
        e-ISSN
        1422-0067
    
 
    
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	    Volume: 22,  
	    Issue: 2,  
	    Pages: ,  
	    Article Number: 801 
	    Supplement: ,  
	
    
 
    
        
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            Publisher
            MDPI
        
 
        
            Publishing Place
            Basel
        
 
	
        
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            0000-00-00
        
 
        
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        Reviewing status
        Peer reviewed
    
 
     
    
        POF-Topic(s)
        30205 - Bioengineering and Digital Health
    
 
    
        Research field(s)
        Enabling and Novel Technologies
    
 
    
        PSP Element(s)
        G-503800-001
    
 
    
        Grants
        the Konung Gustaf V:s 80-årsfond
Swedish Foundation for Strategic Research
    
 
    
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        Erfassungsdatum
        2021-03-26