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The burden of disease associated with filaggrin mutations: a population-based, longitudinal birth cohort study.
- Source :
-
The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2008 Apr; Vol. 121 (4), pp. 872-7.e9. Date of Electronic Publication: 2008 Mar 05. - Publication Year :
- 2008
-
Abstract
- Background: Atopic disease is a major health problem. Mutations in the filaggrin gene (FLG) confer major susceptibility to eczema and related asthma.<br />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.<br />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.<br />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)).<br />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.
- Subjects :
- Alleles
Asthma diagnosis
Asthma genetics
Asthma immunology
Child
Child, Preschool
Cohort Studies
Dermatitis, Atopic diagnosis
Dermatitis, Atopic genetics
Dermatitis, Atopic immunology
Eczema diagnosis
Eczema genetics
Eczema immunology
Female
Filaggrin Proteins
Genetic Predisposition to Disease
Gestational Age
Humans
Hypersensitivity, Immediate diagnosis
Infant
Intermediate Filament Proteins deficiency
Longitudinal Studies
Male
Respiratory Sounds diagnosis
Respiratory Sounds genetics
Respiratory Sounds immunology
Hypersensitivity, Immediate genetics
Hypersensitivity, Immediate immunology
Intermediate Filament Proteins genetics
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1097-6825
- Volume :
- 121
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of allergy and clinical immunology
- Publication Type :
- Academic Journal
- Accession number :
- 18325573
- Full Text :
- https://doi.org/10.1016/j.jaci.2008.01.026