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

    Research output: Contribution to journalArticle

    434 Citations (Scopus)

    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.

    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
    Volume118
    Issue number1
    DOIs
    Publication statusPublished - 1 Jul 2006

    Fingerprint

    Atopic Dermatitis
    Genes
    Ichthyosis Vulgaris
    Mutation
    Skin
    filaggrin
    Skin Diseases
    Causality
    Immunoglobulin E
    Cohort Studies
    Serum

    Keywords

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

    Cite this

    Weidinger, Stephan ; Illig, Thomas ; Baurecht, Hansjörg ; Irvine, Alan D. ; Rodriguez, Elke ; Diaz-Lacava, Amalia ; Klopp, Norman ; Wagenpfeil, Stefan ; Zhao, Yiwei ; Liao, Haihui ; Lee, Simon P. ; Palmer, Colin N A ; Jenneck, Claudia ; Maintz, Laura ; Hagemann, Tobias ; Behrendt, Heidrun ; Ring, Johannes ; Nothen, Markus M. ; McLean, W. H Irwin ; Novak, Natalija. / Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. In: Journal of Allergy and Clinical Immunology. 2006 ; Vol. 118, No. 1. pp. 214-219.
    @article{684bffc10b90439fbab02441f7268ab2,
    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.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.",
    keywords = "Atopic dermatitis, epidermal differentiation complex, filaggrin, polymorphisms, skin barrier",
    author = "Stephan Weidinger and Thomas Illig and Hansj{\"o}rg Baurecht and Irvine, {Alan D.} and Elke Rodriguez and Amalia Diaz-Lacava and Norman Klopp and Stefan Wagenpfeil and Yiwei Zhao and Haihui Liao and Lee, {Simon P.} and Palmer, {Colin N A} and Claudia Jenneck and Laura Maintz and Tobias Hagemann and Heidrun Behrendt and Johannes Ring and Nothen, {Markus M.} and McLean, {W. H Irwin} and Natalija Novak",
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    Weidinger, S, Illig, T, Baurecht, H, Irvine, AD, Rodriguez, E, Diaz-Lacava, A, Klopp, N, Wagenpfeil, S, Zhao, Y, Liao, H, Lee, SP, Palmer, CNA, Jenneck, C, Maintz, L, Hagemann, T, Behrendt, H, Ring, J, Nothen, MM, McLean, WHI & Novak, N 2006, 'Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations', Journal of Allergy and Clinical Immunology, vol. 118, no. 1, pp. 214-219. https://doi.org/10.1016/j.jaci.2006.05.004

    Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. / Weidinger, Stephan; Illig, Thomas; Baurecht, Hansjörg; Irvine, Alan D.; Rodriguez, Elke; Diaz-Lacava, Amalia; Klopp, Norman; Wagenpfeil, Stefan; Zhao, Yiwei; Liao, Haihui; Lee, Simon P.; Palmer, Colin N A; Jenneck, Claudia; Maintz, Laura; Hagemann, Tobias; Behrendt, Heidrun; Ring, Johannes; Nothen, Markus M.; McLean, W. H Irwin; Novak, Natalija.

    In: Journal of Allergy and Clinical Immunology, Vol. 118, No. 1, 01.07.2006, p. 214-219.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations

    AU - Weidinger, Stephan

    AU - Illig, Thomas

    AU - Baurecht, Hansjörg

    AU - Irvine, Alan D.

    AU - Rodriguez, Elke

    AU - Diaz-Lacava, Amalia

    AU - Klopp, Norman

    AU - Wagenpfeil, Stefan

    AU - Zhao, Yiwei

    AU - Liao, Haihui

    AU - Lee, Simon P.

    AU - Palmer, Colin N A

    AU - Jenneck, Claudia

    AU - Maintz, Laura

    AU - Hagemann, Tobias

    AU - Behrendt, Heidrun

    AU - Ring, Johannes

    AU - Nothen, Markus M.

    AU - McLean, W. H Irwin

    AU - Novak, Natalija

    PY - 2006/7/1

    Y1 - 2006/7/1

    N2 - 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.

    AB - 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.

    KW - Atopic dermatitis

    KW - epidermal differentiation complex

    KW - filaggrin

    KW - polymorphisms

    KW - skin barrier

    U2 - 10.1016/j.jaci.2006.05.004

    DO - 10.1016/j.jaci.2006.05.004

    M3 - Article

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    EP - 219

    JO - Journal of Allergy and Clinical Immunology

    JF - Journal of Allergy and Clinical Immunology

    SN - 0091-6749

    IS - 1

    ER -