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Association of Filaggrin loss-of-function-mutations with atopic dermatitis and asthma in the Early Treatment of the Atopic Child (ETAC) population

Authors

  • Sebastian Müller,

    1. Department of Pediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany
    2. Department of Pediatric Nephrology, Charité-Universitätsmedizin Berlin, Berlin, Germany
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    • *

      These authors contributed equally to this work.

  • Ingo Marenholz,

    1. Department of Pediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany
    2. Max-Delbrück-Centrum for Molecular Medicine, Berlin, Germany
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    • *

      These authors contributed equally to this work.

  • Young-Ae Lee,

    1. Department of Pediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany
    2. Max-Delbrück-Centrum for Molecular Medicine, Berlin, Germany
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  • Claudia Sengler,

    1. Department of Pediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany
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  • Simona Eva Zitnik,

    1. Department of Pediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany
    2. University Children’s Hospital, Ljubljana, Slovenia
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  • Rupino W. Griffioen,

    1. Department of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands
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  • Paolo Meglio,

    1. Department of Pediatrics, University “La Sapienza”, Rome, Italy
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  • Ulrich Wahn,

    1. Department of Pediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany
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  • Renate Nickel

    1. Department of Pediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany
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Young-Ae Lee, MD, Pediatric Pneumology and Immunology, Charité, Campus Virchow Klinikum, Augustenburger Platz 1, D-13353 Berlin, Germany
Tel.: +49 30 9406 35 12
Fax: +49 30 9406 31 47
E-mail: yolee@mdc-berlin.de

Abstract

Many candidate gene studies for atopic dermatitis (AD) and associated phenotypes have been conducted so far, but replication of significant results has been a major problem. Two loss of function polymorphisms FLG R501X- and 2282del4, in the Filaggrin (FLG) gene encoding for an epidermal barrier protein were recently identified. They were reported to be predisposing factors for AD and concomitant asthma. Several groups confirmed the initial results in independent populations. The aim of this study is to further investigate the importance of these FLG variants in the development of AD and subsequent asthma symptoms in pre-school children, we investigated children and parents of the Early Treatment of the Atopic Child (ETAC)-trial. We genotyped 496 children and 488 parents of the ETAC population for the two FLG variants, evaluating an association by family based analysis (transmission disequilibrium test). We found a highly significant association of the FLG null variants R501X- and 2282del4 with AD (combined genotype p < 0.0001) and asthma (combined genotype p < 0.0001). The replication and its statistical significance underlines the importance of the FLG polymorphisms and the importance of the skin barrier function in the development of AD and subsequent asthma.

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