DNA methylation and allergic sensitizations: A genome-scale longitudinal study during adolescence.
DNA methylation
adolescence
allergic sensitization
longitudinal
skin prick test
Journal
Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
12
07
2018
revised:
21
12
2018
accepted:
08
01
2019
pubmed:
15
2
2019
medline:
9
6
2020
entrez:
15
2
2019
Statut:
ppublish
Résumé
The presence of allergic sensitization has a major influence on the development and course of common childhood conditions such as asthma and rhinitis. The etiology of allergic sensitization is poorly understood, and its underlying biological mechanisms are not well established. Several studies showed that DNA methylation (DNAm) at some CpGs is associated with allergic sensitization. However, no studies have focused on the critical adolescence period. We assessed the association of pre- and postadolescence genome-wide DNAm with allergic sensitization against indoor, outdoor and food allergens, using linear mixed models. We hypothesized that DNAm is associated with sensitization in general, and with poly-sensitization status, and these associations are age- and gender-specific. We tested these hypotheses in the IoW cohort (n = 376) and examined the findings in the BAMSE cohort (n = 267). Via linear mixed models, we identified 35 CpGs in IoW associated with allergic sensitization (at false discovery rate of 0.05), of which 33 were available in BAMSE and replicated with respect to the direction of associations with allergic sensitization. At the 35 CpGs except for cg19210306 on C13orf27, a reduction in methylation among atopic subjects was observed, most notably for cg21220721 and cg11699125 (ACOT7). DNAm at cg10159529 was strongly correlated with expression of IL5RA in peripheral blood (P-value = 6.76 × 10 In adolescence, the status of allergic sensitization was associated with DNAm differentiation and at some CpGs the association is likely to be age-specific.
Sections du résumé
BACKGROUND
The presence of allergic sensitization has a major influence on the development and course of common childhood conditions such as asthma and rhinitis. The etiology of allergic sensitization is poorly understood, and its underlying biological mechanisms are not well established. Several studies showed that DNA methylation (DNAm) at some CpGs is associated with allergic sensitization. However, no studies have focused on the critical adolescence period.
METHODS
We assessed the association of pre- and postadolescence genome-wide DNAm with allergic sensitization against indoor, outdoor and food allergens, using linear mixed models. We hypothesized that DNAm is associated with sensitization in general, and with poly-sensitization status, and these associations are age- and gender-specific. We tested these hypotheses in the IoW cohort (n = 376) and examined the findings in the BAMSE cohort (n = 267).
RESULTS
Via linear mixed models, we identified 35 CpGs in IoW associated with allergic sensitization (at false discovery rate of 0.05), of which 33 were available in BAMSE and replicated with respect to the direction of associations with allergic sensitization. At the 35 CpGs except for cg19210306 on C13orf27, a reduction in methylation among atopic subjects was observed, most notably for cg21220721 and cg11699125 (ACOT7). DNAm at cg10159529 was strongly correlated with expression of IL5RA in peripheral blood (P-value = 6.76 × 10
CONCLUSION
In adolescence, the status of allergic sensitization was associated with DNAm differentiation and at some CpGs the association is likely to be age-specific.
Identifiants
pubmed: 30762239
doi: 10.1111/all.13746
pmc: PMC6599678
mid: NIHMS1033199
doi:
Substances chimiques
Allergens
0
Immunoglobulin E
37341-29-0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1166-1175Subventions
Organisme : Swedish Heart-Lung Foundation
Pays : International
Organisme : European Union's Horizon 2020 Research and Innovation Programme
ID : 757919
Pays : International
Organisme : Strategic Research Programme (SFO) in Epidemiology at Karolinska Institutet
Pays : International
Organisme : Mechanisms of the Development of ALLergy (MeDALL)
Pays : International
Organisme : NIAID NIH HHS
ID : R01 AI121226
Pays : United States
Organisme : European Framework Programme 7
ID : 261357
Pays : International
Organisme : Swedish Research Council
Pays : International
Organisme : Stockholm County Council
Pays : International
Organisme : NHLBI NIH HHS
ID : R01 HL132321
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI099367
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI091905
Pays : United States
Informations de copyright
© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
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