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Epistasis between FLG and IL4R Genes on the Risk of Allergic Sensitization: Results from Two Population-Based Birth Cohort Studies

Immune-specific 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 effect (gene-gene interaction) between genetic variants within interleuk...

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Autores principales: Ziyab, Ali H., Hankinson, Jenny, Ewart, Susan, Schauberger, Eric, Kopec-Harding, Kamilla, Zhang, Hongmei, Custovic, Adnan, Arshad, Hasan, Simpson, Angela, Karmaus, Wilfried J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818621/
https://www.ncbi.nlm.nih.gov/pubmed/29459738
http://dx.doi.org/10.1038/s41598-018-21459-x
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author Ziyab, Ali H.
Hankinson, Jenny
Ewart, Susan
Schauberger, Eric
Kopec-Harding, Kamilla
Zhang, Hongmei
Custovic, Adnan
Arshad, Hasan
Simpson, Angela
Karmaus, Wilfried J.
author_facet Ziyab, Ali H.
Hankinson, Jenny
Ewart, Susan
Schauberger, Eric
Kopec-Harding, Kamilla
Zhang, Hongmei
Custovic, Adnan
Arshad, Hasan
Simpson, Angela
Karmaus, Wilfried J.
author_sort Ziyab, Ali H.
collection PubMed
description Immune-specific 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 effect (gene-gene interaction) between genetic variants within interleukin 4 receptor (IL4R) and filaggrin (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 significance (interaction term: P = 0.003). To illustrate the observed epistasis, stratified 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 effect 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.
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spelling pubmed-58186212018-02-26 Epistasis between FLG and IL4R Genes on the Risk of Allergic Sensitization: Results from Two Population-Based Birth Cohort Studies Ziyab, Ali H. Hankinson, Jenny Ewart, Susan Schauberger, Eric Kopec-Harding, Kamilla Zhang, Hongmei Custovic, Adnan Arshad, Hasan Simpson, Angela Karmaus, Wilfried J. Sci Rep Article Immune-specific 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 effect (gene-gene interaction) between genetic variants within interleukin 4 receptor (IL4R) and filaggrin (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 significance (interaction term: P = 0.003). To illustrate the observed epistasis, stratified 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 effect 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. Nature Publishing Group UK 2018-02-19 /pmc/articles/PMC5818621/ /pubmed/29459738 http://dx.doi.org/10.1038/s41598-018-21459-x Text en © The Author(s) 2018 Open Access 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. The 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/.
spellingShingle Article
Ziyab, Ali H.
Hankinson, Jenny
Ewart, Susan
Schauberger, Eric
Kopec-Harding, Kamilla
Zhang, Hongmei
Custovic, Adnan
Arshad, Hasan
Simpson, Angela
Karmaus, Wilfried J.
Epistasis between FLG and IL4R Genes on the Risk of Allergic Sensitization: Results from Two Population-Based Birth Cohort Studies
title Epistasis between FLG and IL4R Genes on the Risk of Allergic Sensitization: Results from Two Population-Based Birth Cohort Studies
title_full Epistasis between FLG and IL4R Genes on the Risk of Allergic Sensitization: Results from Two Population-Based Birth Cohort Studies
title_fullStr Epistasis between FLG and IL4R Genes on the Risk of Allergic Sensitization: Results from Two Population-Based Birth Cohort Studies
title_full_unstemmed Epistasis between FLG and IL4R Genes on the Risk of Allergic Sensitization: Results from Two Population-Based Birth Cohort Studies
title_short Epistasis between FLG and IL4R Genes on the Risk of Allergic Sensitization: Results from Two Population-Based Birth Cohort Studies
title_sort epistasis between flg and il4r genes on the risk of allergic sensitization: results from two population-based birth cohort studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818621/
https://www.ncbi.nlm.nih.gov/pubmed/29459738
http://dx.doi.org/10.1038/s41598-018-21459-x
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