title: Loss-of-function variants of the filaggrin gene are associated with atopic eczema and associated phenotypes in Swedish families.
abstract: Recent studies have identified 2 loss-of-function variants, R501X and 2282del4, in the filaggrin gene as predisposing factors in the development of eczema. In this study, representing the first analysis of the variants in a Swedish population, we analysed transmission in 406 multiplex eczema families with mainly adult patients. In accordance with previous studies we found association between the filaggrin gene variants and atopic eczema (p=9.5 x 10(-8)). The highest odds ratio for the combined allele, 4.73 (1.98-11.29), p=3.6 x 10(-8), was found for the subgroup with a severe eczema phenotype, and association was also found with raised allergen-specific IgE, allergic asthma and allergic rhinoconjunctivitis occurring in the context of eczema. Our results support an important role for the filaggrin gene variants R501X and 2282del4 in the development and severity of atopic eczema and indicate a possible role for the subsequent progression into eczema-associated phenotypes.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. Elisabeth.Ekelund@ki.se
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ekelund
authors.forename: Agne
authors.initials: A
authors.lastname: Liedén
authors.forename: Jenny
authors.initials: J
authors.lastname: Link
authors.forename: Simon P
authors.initials: SP
authors.lastname: Lee
authors.forename: Mauro
authors.initials: M
authors.lastname: D'Amato
authors.forename: Colin N A
authors.initials: CN
authors.lastname: Palmer
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kockum
authors.forename: Maria
authors.initials: M
authors.lastname: Bradley
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D004485:Eczema / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D000091344:Filaggrin Proteins; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007223:Infant; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000502:physiology; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D006255:Rhinitis, Allergic, Seasonal / Q000235:genetics; D013548:Sweden
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D007073:Immunoglobulin E