title: Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations.
abstract: BACKGROUND
  Atopic dermatitis (AD) is a chronic inflammatory skin disease with a strong genetic background. One of the characteristic features of AD and causative factor for the disease is an impaired epidermal skin barrier based on a primary defect of epidermal differentiation.
  
  
  OBJECTIVE
  Recently, 2 loss-of-function mutations (R501X and 2282derl4) in the filaggrin gene (FLG) that cause ichthyosis vulgaris, one of the most common inherited skin disorders of keratinization, have been reported to be strong predisposing factors for AD.
  
  
  METHODS
  We evaluated the association of the loss-of-function mutations R501X and 2282del4 within the FLG gene in a large collection of 476 well-characterized white German families with AD by using the transmission-disequilibrium test.
  
  
  RESULTS
  Our family-based approach revealed prominent associations between the 2 loss-of-function FLG mutations and AD, as previously observed in a traditional Mendelian linkage analysis and case-control cohort analysis approach. In addition, we observed associations of the FLG mutations in particular with the extrinsic subtype of AD, which is characterized by high total serum IgE levels and concomitant allergic sensitizations. Furthermore, FLG mutations are significantly associated with palmar hyperlinearity in patients with AD, which represents a shared feature of AD and ichthyosis vulgaris.
  
  
  CONCLUSIONS
  Together these data implicate that FLG is the first really strong genetic factor identified in a common complex disease.
  
  
  CONCLUSIONS
  These findings underline the crucial role of the skin barrier in preventing allergic sensitization.
authors.affiliation: Department of Dermatology and Allergy Biederstein, Technical University Munich, Biedersteiner Strasse 29, 80802 Munich, Germany. weidinger@lrz.tum.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Weidinger
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Baurecht
authors.forename: Alan D
authors.initials: AD
authors.lastname: Irvine
authors.forename: Elke
authors.initials: E
authors.lastname: Rodriguez
authors.forename: Amalia
authors.initials: A
authors.lastname: Diaz-Lacava
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagenpfeil
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Zhao
authors.forename: Haihui
authors.initials: H
authors.lastname: Liao
authors.forename: Simon P
authors.initials: SP
authors.lastname: Lee
authors.forename: Colin N A
authors.initials: CN
authors.lastname: Palmer
authors.forename: Claudia
authors.initials: C
authors.lastname: Jenneck
authors.forename: Laura
authors.initials: L
authors.lastname: Maintz
authors.forename: Tobias
authors.initials: T
authors.lastname: Hagemann
authors.forename: Heidrun
authors.initials: H
authors.lastname: Behrendt
authors.forename: Johannes
authors.initials: J
authors.lastname: Ring
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nothen
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
authors.forename: Natalija
authors.initials: N
authors.lastname: Novak
mesh_terms: D016022:Case-Control Studies; D003876:Dermatitis, Atopic / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007381:Intermediate Filament Proteins / Q000235:genetics*; D009154:Mutation; D012867:Skin / Q000378:metabolism
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D007073:Immunoglobulin E