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Analysis of the high affinity IgE receptor genes reveals epistatic effects of FCER1A variants on eczema risk

Authors

  • J. M. Mahachie John,

    1. Systems and Modeling Unit, Department of Electrical Engineering and Computer Science, University of Liège, Liège, Belgium
    2. Bioinformatics and Modeling, GIGA, University of Liège, Liège, Belgium
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    • *

      These authors contributed equally.

  • H. Baurecht,

    1. Bioinformatics and Modeling, GIGA, University of Liège, Liège, Belgium
    2. Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
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    • *

      These authors contributed equally.

  • E. Rodríguez,

    1. Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
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  • A. Naumann,

    1. Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
    2. Institute for Medical Statistics and Epidemiology IMSE, Technische Universität München, Munich, Germany
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  • S. Wagenpfeil,

    1. Institute for Medical Statistics and Epidemiology IMSE, Technische Universität München, Munich, Germany
    2. Graduate School of Information Science in Health (GSISH), Technische Universität München, Munich, Germany
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  • N. Klopp,

    1. Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
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  • M. Mempel,

    1. Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
    2. ZAUM – Center for Allergy and Environment, Division of Environmental Dermatology and Allergy, Helmholtz Zentrum/Technische Universität München, Munich, Germany
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  • N. Novak,

    1. Department of Dermatology and Allergy, University of Bonn, Bonn, Germany
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  • T. Bieber,

    1. Department of Dermatology and Allergy, University of Bonn, Bonn, Germany
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  • H.-E. Wichmann,

    1. Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
    2. Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany
    3. Klinikum Grosshadern, Munich, Germany
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  • J. Ring,

    1. Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
    2. ZAUM – Center for Allergy and Environment, Division of Environmental Dermatology and Allergy, Helmholtz Zentrum/Technische Universität München, Munich, Germany
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  • T. Illig,

    1. Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
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  • T. Cattaert,

    1. Systems and Modeling Unit, Department of Electrical Engineering and Computer Science, University of Liège, Liège, Belgium
    2. Bioinformatics and Modeling, GIGA, University of Liège, Liège, Belgium
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  • K. Van Steen,

    1. Systems and Modeling Unit, Department of Electrical Engineering and Computer Science, University of Liège, Liège, Belgium
    2. Bioinformatics and Modeling, GIGA, University of Liège, Liège, Belgium
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  • S. Weidinger

    1. Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
    2. ZAUM – Center for Allergy and Environment, Division of Environmental Dermatology and Allergy, Helmholtz Zentrum/Technische Universität München, Munich, Germany
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  • Edited by: Hans-Uwe Simon

Stephan Weidinger, MD, Department of Dermatology and Allergy Biederstein, Technische Universität München, Biedersteiner Str. 29, 80802 Munich, Germany.
Tel: +0049 89 4140 3170
Fax: +0049 89 4140 3171
E-mail: weidinger@lrz.tum.de

Abstract

To cite this article: Mahachie John JM, Baurecht H, Rodríguez E, Naumann A, Wagenpfeil S, Klopp N, Mempel M, Novak N, Bieber T, Wichmann H-E, Ring J, Illig T, Cattaert T, Van Steen K, Weidinger S. Analysis of the high affinity IgE receptor genes reveals epistatic effects of FCER1A variants eczema risk. Allergy 2010; 65: 875–882.

Abstract

Background:  High levels of total and allergen-specific IgE levels are a key feature in allergic diseases. The high-affinity receptor for IgE, which is composed of one alpha (FCER1A), one beta (FCER1B), and two gamma (FCER1G) subunits, represents the central receptor of IgE-induced reactions. In a genome-wide association scan, we recently identified associations between functional FCER1A variants and total serum IgE levels. Previous studies had reported linkage and association of FCER1B variants with IgE and atopic traits. The FCER1G gene has not yet been investigated with regard to atopy. Filaggrin (FLG) is the strongest known risk gene for eczema, in particular the allergic subtype of eczema.

Methods:  We investigated the association of FCER1A, FCER1B, and FCER1G variants with IgE in a large population-based cohort (n = 4261) and tested for epistatic effects using the model-based multifactor dimensionality reduction (MB-MDR) method. In addition, we investigated a potential interaction between FLG and FCER1A variants in a large collection of eczema cases (n = 1018) and population controls.

Results:  Three strongly correlated FCER1A polymorphisms were significantly associated with total and specific IgE levels as well as allergic sensitization. No associations were seen for FCER1B and FCER1G. After adjustment for FLG effects, a significant epistatic effect of the FCER1A variants rs10489854 and rs2511211 on eczema risk was detected.

Conclusions:  These results suggest that FCER1A variants by themselves and in combination influence IgE levels and act synergistically to influence eczema risk.

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