Analysis of the high affinity IgE receptor genes reveals epistatic effects of FCER1A variants on eczema risk
J. M. Mahachie John
Systems and Modeling Unit, Department of Electrical Engineering and Computer Science, University of Liège, Liège, Belgium
Bioinformatics and Modeling, GIGA, University of Liège, Liège, Belgium
These authors contributed equally.
Search for more papers by this authorH. Baurecht
Bioinformatics and Modeling, GIGA, University of Liège, Liège, Belgium
Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
These authors contributed equally.
Search for more papers by this authorE. Rodríguez
Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
Search for more papers by this authorA. Naumann
Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
Institute for Medical Statistics and Epidemiology IMSE, Technische Universität München, Munich, Germany
Search for more papers by this authorS. Wagenpfeil
Institute for Medical Statistics and Epidemiology IMSE, Technische Universität München, Munich, Germany
Graduate School of Information Science in Health (GSISH), Technische Universität München, Munich, Germany
Search for more papers by this authorN. Klopp
Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
Search for more papers by this authorM. Mempel
Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
ZAUM – Center for Allergy and Environment, Division of Environmental Dermatology and Allergy, Helmholtz Zentrum/Technische Universität München, Munich, Germany
Search for more papers by this authorN. Novak
Department of Dermatology and Allergy, University of Bonn, Bonn, Germany
Search for more papers by this authorT. Bieber
Department of Dermatology and Allergy, University of Bonn, Bonn, Germany
Search for more papers by this authorH.-E. Wichmann
Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany
Klinikum Grosshadern, Munich, Germany
Search for more papers by this authorJ. Ring
Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
ZAUM – Center for Allergy and Environment, Division of Environmental Dermatology and Allergy, Helmholtz Zentrum/Technische Universität München, Munich, Germany
Search for more papers by this authorT. Illig
Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
Search for more papers by this authorT. Cattaert
Systems and Modeling Unit, Department of Electrical Engineering and Computer Science, University of Liège, Liège, Belgium
Bioinformatics and Modeling, GIGA, University of Liège, Liège, Belgium
Search for more papers by this authorK. Van Steen
Systems and Modeling Unit, Department of Electrical Engineering and Computer Science, University of Liège, Liège, Belgium
Bioinformatics and Modeling, GIGA, University of Liège, Liège, Belgium
Search for more papers by this authorS. Weidinger
Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
ZAUM – Center for Allergy and Environment, Division of Environmental Dermatology and Allergy, Helmholtz Zentrum/Technische Universität München, Munich, Germany
Search for more papers by this authorJ. M. Mahachie John
Systems and Modeling Unit, Department of Electrical Engineering and Computer Science, University of Liège, Liège, Belgium
Bioinformatics and Modeling, GIGA, University of Liège, Liège, Belgium
These authors contributed equally.
Search for more papers by this authorH. Baurecht
Bioinformatics and Modeling, GIGA, University of Liège, Liège, Belgium
Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
These authors contributed equally.
Search for more papers by this authorE. Rodríguez
Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
Search for more papers by this authorA. Naumann
Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
Institute for Medical Statistics and Epidemiology IMSE, Technische Universität München, Munich, Germany
Search for more papers by this authorS. Wagenpfeil
Institute for Medical Statistics and Epidemiology IMSE, Technische Universität München, Munich, Germany
Graduate School of Information Science in Health (GSISH), Technische Universität München, Munich, Germany
Search for more papers by this authorN. Klopp
Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
Search for more papers by this authorM. Mempel
Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
ZAUM – Center for Allergy and Environment, Division of Environmental Dermatology and Allergy, Helmholtz Zentrum/Technische Universität München, Munich, Germany
Search for more papers by this authorN. Novak
Department of Dermatology and Allergy, University of Bonn, Bonn, Germany
Search for more papers by this authorT. Bieber
Department of Dermatology and Allergy, University of Bonn, Bonn, Germany
Search for more papers by this authorH.-E. Wichmann
Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany
Klinikum Grosshadern, Munich, Germany
Search for more papers by this authorJ. Ring
Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
ZAUM – Center for Allergy and Environment, Division of Environmental Dermatology and Allergy, Helmholtz Zentrum/Technische Universität München, Munich, Germany
Search for more papers by this authorT. Illig
Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
Search for more papers by this authorT. Cattaert
Systems and Modeling Unit, Department of Electrical Engineering and Computer Science, University of Liège, Liège, Belgium
Bioinformatics and Modeling, GIGA, University of Liège, Liège, Belgium
Search for more papers by this authorK. Van Steen
Systems and Modeling Unit, Department of Electrical Engineering and Computer Science, University of Liège, Liège, Belgium
Bioinformatics and Modeling, GIGA, University of Liège, Liège, Belgium
Search for more papers by this authorS. Weidinger
Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
ZAUM – Center for Allergy and Environment, Division of Environmental Dermatology and Allergy, Helmholtz Zentrum/Technische Universität München, Munich, Germany
Search for more papers by this authorEdited by: Hans-Uwe Simon
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.
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.
Supporting Information
Supplementary Methods.
Table S1. FCER1A variants, primers, call rates/number of individuals typed successfully and minor allele frequencies (MAFs).
Table S2. FCER1B, FCER1G and FLG variants, primers, call rates/number of individuals typed successfully and minor allele frequencies (MAFs).
Table S3. Primers, call rates/number of individuals typed successfully, and minor allele frequencies (MAFs) of FCER1A and FLG variants in the case control cohort.
Table S4. Association results for all FCER1A and FLG variants tested in the cross sectional case-control cohort.
Table S5. Subanalyses of the association of FCER1A variants and IgE levels in atopic (n = 1116) and a non-atopic (n = 3012) individuals of the KORA cross-sectional cohort (n = 4261).
Please note: Wiley-Blackwell are not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article.
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