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http://purl.uniprot.org/citations/17030239http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17030239http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17030239http://www.w3.org/2000/01/rdf-schema#comment"

Background

Childhood eczema often precedes the development of asthma and allergic rhinitis in the so-called atopic march. Recently, 2 loss-of-function mutations in the gene encoding the epidermal barrier protein filaggrin were reported to be predisposing factors for eczema and concomitant asthma, suggesting a possible role in disease transition.

Objective

We aimed to assess the importance of filaggrin loss-of-function mutations in the susceptibility to eczema and associated clinical phenotypes.

Methods

The filaggrin mutations were genotyped and tested for association with allergic disorders in 2 large European populations including 1092 children with eczema.

Results

Highly significant association of the filaggrin null mutations with eczema and concomitant asthma was replicated. Moreover, we found that these mutations predispose to asthma, allergic rhinitis, and allergic sensitization only in the presence of eczema. We show that the presence of 2 filaggrin null alleles is an independent risk factor for asthma in children with eczema, and that the 2 investigated mutations account for about 11% of eczema cases in the German population.

Conclusion

These results lend strong support to the role of filaggrin in the pathogenesis of eczema and in the subsequent progression along the atopic march. The fact that previous expression of eczema is a prerequisite for the manifestation of allergic airways disease and specific sensitization highlights the importance of the epidermal barrier in the pathogenesis of these disorders.

Clinical implications

Our results suggest that the maintenance and repair of the epidermal barrier in infants with eczema may prevent the subsequent development of allergic airways disease."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.org/dc/terms/identifier"doi:10.1016/j.jaci.2006.07.026"xsd:string
http://purl.uniprot.org/citations/17030239http://purl.org/dc/terms/identifier"doi:10.1016/j.jaci.2006.07.026"xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Lee Y.-A."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Lee Y.-A."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Wahn U."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Wahn U."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Nickel R."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Nickel R."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Marenholz I."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Marenholz I."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Rueschendorf F."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Rueschendorf F."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Lau S."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Lau S."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Schulz F."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Schulz F."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Keil T."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Keil T."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Esparza-Gordillo J."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Esparza-Gordillo J."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Kerscher T."xsd:string
http://purl.uniprot.org/citations/17030239http://purl.uniprot.org/core/author"Kerscher T."xsd:string
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