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  • Title: Filaggrin mutations confer susceptibility to atopic dermatitis but not to asthma.
    Author: Rogers AJ, Celedón JC, Lasky-Su JA, Weiss ST, Raby BA.
    Journal: J Allergy Clin Immunol; 2007 Dec; 120(6):1332-7. PubMed ID: 18073125.
    Abstract:
    BACKGROUND: Loss-of-function mutations in the filaggrin gene (FLG) have been strongly associated with atopic dermatitis and allergic phenotypes in multiple populations. The role of these mutations in the development of asthma is less clear, particularly in patients who do not have coincident atopic dermatitis. OBJECTIVE: To determine whether FLG mutations are associated with asthma or asthma-related intermediate phenotypes. METHODS: We genotyped 2 loss-of-function FLG mutations (R501X and 2282del4) in white children (age 5-12 years) with mild to moderate asthma in the Childhood Asthma Management Program. We assessed the relationship of these mutations to asthma and allergy-related phenotypes in children with and without atopic dermatitis using both population-based and family-based tests of association. RESULTS: Nearly 1/3 (185/646) of the participating children had atopic dermatitis. Although strong associations were observed between FLG mutations and atopic dermatitis (odds ratio, 2.4; P = 7.6 x 10(-5)) and between the mutations and total serum IgE level (P = .009 in the atopic dermatitis cohort), no association was noted with either asthma or asthma-related phenotypes, including FEV(1), FEV(1)/forced vital capacity, and methacholine PC(20) (P > .1 for all tests). CONCLUSION: Although FLG loss-of-function mutations are consistently associated with atopic dermatitis and other allergic phenotypes, these mutations do not appear to influence either susceptibility to asthma or asthma severity phenotypes. CLINICAL IMPLICATIONS: Filaggrin mutations that predispose to atopic dermatitis do not modulate the asthma phenotype.
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