Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations

Stephan Weidinger, Thomas Illig, Hansjörg Baurecht, Alan D. Irvine, Elke Rodriguez, Amalia Diaz-Lacava, Norman Klopp, Stefan Wagenpfeil, Yiwei Zhao, Haihui Liao, Simon P. Lee, Colin N A Palmer, Claudia Jenneck, Laura Maintz, Tobias Hagemann, Heidrun Behrendt, Johannes Ring, Markus M. Nothen, W. H Irwin McLean, Natalija Novak

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    486 Citations (Scopus)


    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.

    Objectives: 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.

    Conclusion: Together these data implicate that FLG is the first really strong genetic factor identified in a common complex disease. Clinical implications: These findings underline the crucial role of the skin barrier in preventing allergic sensitization.

    Original languageEnglish
    Pages (from-to)214-219
    Number of pages6
    JournalJournal of Allergy and Clinical Immunology
    Issue number1
    Publication statusPublished - 1 Jul 2006


    • Atopic dermatitis
    • epidermal differentiation complex
    • filaggrin
    • polymorphisms
    • skin barrier


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