The burden of disease associated with filaggrin mutations: A population-based, longitudinal birth cohort study

John Henderson, Kate Northstone, Simon P. Lee, Haihui Liao, Yiwei Zhao, Marcus Pembrey, Somnath Mukhopadhyay, George Davey Smith, Colin N. A. Palmer, W. H. Irwin McLean, Alan D. Irvine

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    Abstract

    Background: Atopic disease is a major health problem. Mutations in the filaggrin gene (FLG) confer major susceptibility to eczema and related asthma.

    Objective: We sought to determine the natural history and burden of atopic disease conferred by the 2 most common FLG mutations in a large, population-based birth cohort study.

    Methods: We analyzed the effect of the most common null alleles (R501X and 2282del4) on several atopic phenotypes in a cohort of approximately 7000 English children born in 1990-1991.

    Results: FLG null alleles associated strongly with eczema; eczema associated with these mutations presents in early life and is more persistent (hazard ratio for eczema resolution for those with FLG mutations to FLG wild type, 0.67; 95% CI, 0.58-0.77; P = 5 x 10(-8)). FLG mutations conferred a population asthma risk of 1.80 (95% CI, 1.34-2.41; P = .00019); asthma risk was especially high in the context of eczema (odds ratio, 3.16; 95% CI, 2.25-4.43; P = 1.4 x 10(-11)). Strong associations were identified with sensitization to grass, house dust mite, and cat dander and sensitization to multiple allergens (odds ratio, 2.12; 95% CI, 1.03-4.37; P = 5.42 x 10(-27)).

    Conclusion: FLG mutations are strong genetic determinants of eczema, early wheeze, asthma in the context of eczema, and atopic sensitization. They confer risk of a particular trajectory for eczema, with increased duration of disease and greater risk of asthma and multiple allergic sensitizations. FLG alleles help define the risk profile of children with eczema and help define the "eczema plus early wheeze" and "eczema plus asthma" phenotypes.

    Original languageEnglish
    Pages (from-to)872-877
    Number of pages6
    JournalJournal of Allergy and Clinical Immunology
    Volume121
    Issue number4
    DOIs
    Publication statusPublished - Apr 2008

    Keywords

    • eczema
    • atopic dermatitis
    • asthma
    • skin barrier
    • filaggrin
    • birth cohort
    • atopy
    • ATOPIC-DERMATITIS
    • BRONCHIAL RESPONSIVENESS
    • BARRIER
    • METHODOLOGY
    • PHENOTYPES
    • CHILDREN
    • ALSPAC
    • ASTHMA
    • ECZEMA
    • GENE

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