Dataset Information

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

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.

SUBMITTER: Ziyab AH

PROVIDER: S-EPMC5818621 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

Ziyab Ali H AH Hankinson Jenny J Ewart Susan S Schauberger Eric E Kopec-Harding Kamilla K Zhang Hongmei H Custovic Adnan A Arshad Hasan H Simpson Angela A Karmaus Wilfried J WJ

Scientific reports 20180219 1

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 ...[more]

PMID: 29459738

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Project description:The term "atopic march" has been used to imply a natural progression of a cascade of symptoms from eczema to asthma and rhinitis through childhood. We hypothesize that this expression does not adequately describe the natural history of eczema, wheeze, and rhinitis during childhood. We propose that this paradigm arose from cross-sectional analyses of longitudinal studies, and may reflect a population pattern that may not predominate at the individual level.Data from 9,801 children in two population-based birth cohorts were used to determine individual profiles of eczema, wheeze, and rhinitis and whether the manifestations of these symptoms followed an atopic march pattern. Children were assessed at ages 1, 3, 5, 8, and 11 y. We used Bayesian machine learning methods to identify distinct latent classes based on individual profiles of eczema, wheeze, and rhinitis. This approach allowed us to identify groups of children with similar patterns of eczema, wheeze, and rhinitis over time. Using a latent disease profile model, the data were best described by eight latent classes: no disease (51.3%), atopic march (3.1%), persistent eczema and wheeze (2.7%), persistent eczema with later-onset rhinitis (4.7%), persistent wheeze with later-onset rhinitis (5.7%), transient wheeze (7.7%), eczema only (15.3%), and rhinitis only (9.6%). When latent variable modelling was carried out separately for the two cohorts, similar results were obtained. Highly concordant patterns of sensitisation were associated with different profiles of eczema, rhinitis, and wheeze. The main limitation of this study was the difference in wording of the questions used to ascertain the presence of eczema, wheeze, and rhinitis in the two cohorts.The developmental profiles of eczema, wheeze, and rhinitis are heterogeneous; only a small proportion of children (? 7% of those with symptoms) follow trajectory profiles resembling the atopic march. Please see later in the article for the Editors' Summary.

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Dataset Information

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

Publications

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

Similar Datasets

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