Epistasis between FLG and IL4R genes on the risk of allergic sensitization: results from two population-based birth cohort studies
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Author(s)
Type
Journal Article
Abstract
Immune-specifc genes as well as genes responsible for the formation and integrity of the epidermal
barrier have been implicated in the pathogeneses of allergic sensitization. This study sought to
determine whether an epistatic efect (gene-gene interaction) between genetic variants within
interleukin 4 receptor (IL4R) and flaggrin (FLG) genes predispose to the development of allergic
sensitization. Data from two birth cohort studies were analyzed, namely the Isle of Wight (IOW;
n=1,456) and the Manchester Asthma and Allergy Study (MAAS; n=1,058). In the IOW study, one
interaction term (IL4R rs3024676×FLG variants) showed statistical signifcance (interaction term:
P=0.003). To illustrate the observed epistasis, stratifed analyses were performed, which showed that
FLG variants were associated with allergic sensitization only among IL4R rs3024676 homozygotes (OR,
1.97; 95% CI, 1.27–3.05; P=0.003). In contrast, FLG variants efect was masked among IL4R rs3024676
heterozygotes (OR, 0.53; 95% CI, 0.22–1.32; P=0.175). Similar results were demonstrated in the MAAS
study. Epistasis between immune (IL4R) and skin (FLG) regulatory genes exist in the pathogenesis of
allergic sensitization. Hence, genetic susceptibility towards defective epidermal barrier and deviated
immune responses could work together in the development of allergic sensitization.
barrier have been implicated in the pathogeneses of allergic sensitization. This study sought to
determine whether an epistatic efect (gene-gene interaction) between genetic variants within
interleukin 4 receptor (IL4R) and flaggrin (FLG) genes predispose to the development of allergic
sensitization. Data from two birth cohort studies were analyzed, namely the Isle of Wight (IOW;
n=1,456) and the Manchester Asthma and Allergy Study (MAAS; n=1,058). In the IOW study, one
interaction term (IL4R rs3024676×FLG variants) showed statistical signifcance (interaction term:
P=0.003). To illustrate the observed epistasis, stratifed analyses were performed, which showed that
FLG variants were associated with allergic sensitization only among IL4R rs3024676 homozygotes (OR,
1.97; 95% CI, 1.27–3.05; P=0.003). In contrast, FLG variants efect was masked among IL4R rs3024676
heterozygotes (OR, 0.53; 95% CI, 0.22–1.32; P=0.175). Similar results were demonstrated in the MAAS
study. Epistasis between immune (IL4R) and skin (FLG) regulatory genes exist in the pathogenesis of
allergic sensitization. Hence, genetic susceptibility towards defective epidermal barrier and deviated
immune responses could work together in the development of allergic sensitization.
Date Issued
2018-02-19
Date Acceptance
2018-02-05
Citation
Scientific Reports, 2018, 8
ISSN
2045-2322
Publisher
Nature Publishing Group
Journal / Book Title
Scientific Reports
Volume
8
Copyright Statement
© The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor
Medical Research Council (MRC)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000425380900004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
MR/K002449/1
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
GENOME-WIDE ASSOCIATION
CUTANEOUS SENSITIZATION
ASTHMA
VARIANTS
METAANALYSIS
HETEROSIS
FILAGGRIN
GENETICS
CHILDREN
DISEASES
Publication Status
Published
Article Number
ARTN 3221