Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis.
Nat Genet
; 38(4): 441-6, 2006 Apr.
Article
em En
| MEDLINE
| ID: mdl-16550169
ABSTRACT
Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease.
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Bases de dados:
MEDLINE
Assunto principal:
Fenômenos Fisiológicos da Pele
/
Dermatite Atópica
/
Proteínas de Filamentos Intermediários
/
Mutação
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Child
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Nat Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Reino Unido