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Epistasis between FLG and IL4R genes on the risk of allergic sensitization: Results from two population-based birth cohort studies

Epistasis between FLG and IL4R genes on the risk of allergic sensitization: Results from two population-based birth cohort studies
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 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.

2045-2322
Ziyab, Ali H.
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Hankinson, Jenny
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Ewart, Susan
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Schauberger, Eric
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Kopec-Harding, Kamilla
031a0e41-87ca-4965-bbe0-e962e085c511
Zhang, Hongmei
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Custovic, Adnan
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Arshad, Hasan
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Simpson, Angela
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Karmaus, Wilfried J.
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Ziyab, Ali H.
12905e44-3fd1-47c2-98e5-35320e89815b
Hankinson, Jenny
d6b90901-1910-48b7-a54d-f7789e93e85b
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Schauberger, Eric
465a4658-a065-470e-b7dc-0b713f911922
Kopec-Harding, Kamilla
031a0e41-87ca-4965-bbe0-e962e085c511
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Custovic, Adnan
17d8d092-73b8-44fb-bf48-5cea7b29e3fc
Arshad, Hasan
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Simpson, Angela
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Karmaus, Wilfried J.
1fa55055-6bbd-446c-b8df-61a2d2c34b9c

Ziyab, Ali H., Hankinson, Jenny, Ewart, Susan, Schauberger, Eric, Kopec-Harding, Kamilla, Zhang, Hongmei, Custovic, Adnan, Arshad, Hasan, Simpson, Angela and Karmaus, Wilfried J. (2018) Epistasis between FLG and IL4R genes on the risk of allergic sensitization: Results from two population-based birth cohort studies. Scientific Reports, 8 (1), [3221]. (doi:10.1038/s41598-018-21459-x).

Record type: Article

Abstract

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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s41598-018-21459-x - Version of Record
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Accepted/In Press date: 5 February 2018
e-pub ahead of print date: 19 February 2018
Published date: 1 December 2018

Identifiers

Local EPrints ID: 418389
URI: http://eprints.soton.ac.uk/id/eprint/418389
ISSN: 2045-2322
PURE UUID: 94d24ec6-2919-4514-a5db-627ec2216219

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Date deposited: 06 Mar 2018 17:30
Last modified: 15 Mar 2024 18:45

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Contributors

Author: Ali H. Ziyab
Author: Jenny Hankinson
Author: Susan Ewart
Author: Eric Schauberger
Author: Kamilla Kopec-Harding
Author: Hongmei Zhang
Author: Adnan Custovic
Author: Hasan Arshad
Author: Angela Simpson
Author: Wilfried J. Karmaus

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