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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:121

Article

Henderson, John²  Northstone, Kate³  Lee, Simon P.⁵  Liao, Haihui⁷  Zhao, Yiwei⁷  Pembrey, Marcus⁸  Mukhopadhyay, Somnath⁶  Smith, George Davey⁴  Palmer, Colin N. A.⁵  McLean, W. H. Irwin⁷  Irvine, Alan D.¹ 

[1] Our Ladys Childrens Hosp Crumlin, Dept Paediat Dermatol, Dublin 12, Ireland

[2] Univ Bristol, Dept Community Based Med, Bristol BS8 1TH, Avon, England

[3] Univ Bristol, Dept Social Med, Bristol BS8 1TH, Avon, England

[4] Univ Bristol, MRC, Ctr Causal Anal Translat Epidemiol, Bristol BS8 1TH, Avon, England

[5] Univ Dundee, Populat Pharmacogenet Grp, Biomed Res Ctr, Dundee DD1 4HN, Scotland

[6] Univ Dundee, Childrens Asthma & Allergy Res Unit, Dundee DD1 4HN, Scotland

[7] Univ Dundee, Epithelial Genet Grp, Human Genet Unit, Div Pathol & Neurosci, Dundee DD1 4HN, Scotland

[8] UCL, Inst Child Hlth, London WC1E 6BT, England

关键词: eczema;    atopic dermatitis;    asthma;    skin barrier;    filaggrin;    birth cohort;    atopy;   

DOI  :  10.1016/j.jaci.2008.01.026

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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