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Common variants in FCER1A influence total serum IgE levels from cord blood up to six years of life

Authors

  • C.-M. Chen,

    1. Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Epidemiology, Neuherberg, Germany
    2. Ludwig-Maximilians, University of Munich, Dr von Hauner Children’s Hospital, Munich, Germany
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    • *

      C.-M. Chen and S. Weidinger contributed equally to this work.

  • S. Weidinger,

    1. Department of Dermatology and Allergy, Technical University Munich (TUM), Munich, Germany
    2. Division of Environmental Dermatology and Allergy, Helmholtz Zentrum München, Neuherberg and ZAUM, Center for Allergy and Environment, Technical University Munich (TUM), Munich, Germany
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  • N. Klopp,

    1. Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Epidemiology, Neuherberg, Germany
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  • S. Sausenthaler,

    1. Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Epidemiology, Neuherberg, Germany
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  • W. Bischof,

    1. Department of Indoor Climatology (ark), Institute of Occupational, Social and Environmental Medicine, Friedrich-Schiller-University of Jena, Jena, Germany
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  • O. Herbarth,

    1. Department of Human Exposure Research and Epidemiology, UFZ, Centre for Environmental Research Leipzig, Leipzig, Germany
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  • M. Bauer,

    1. Department of Human Exposure Research and Epidemiology, UFZ, Centre for Environmental Research Leipzig, Leipzig, Germany
    2. Department of Environmental Medicine and Hygiene, Faculty of Medicine, University Leipzig, Germany
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  • M. Borte,

    1. Klinik für Kinder -und Jugendmedizin, Städt. Klinikum “St.Georg” Leipzig, Akademisches Lehrkrankhaus der Universität Leipzig, Leipzig, Germany
    2. Department of Paediatrics, University of Leipzig, Leipzig, Germany
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  • B. Schaaf,

    1. Pediatric Outpatient Department, Bad Honnef, Germany
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  • I. Lehmann,

    1. Department of Environmental Immunology Helmholtz Centre for Environmental Research-UFZ Leipzig, Germany
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  • H. Behrendt,

    1. Department of Environmental Immunology Helmholtz Centre for Environmental Research-UFZ Leipzig, Germany
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  • U. Krämer,

    1. IUF, Institut für Umweltmedizinische Forschung, Düsseldorf, Germany
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  • D. Berdel,

    1. Marien-Hospital Wesel, Wesel, Germany
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  • A. Von Berg,

    1. Marien-Hospital Wesel, Wesel, Germany
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  • C. P. Bauer,

    1. Kinderklinik und Poliklinik, Munich Technical University, Munich, Germany
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  • S. Koletzko,

    1. Kinderklinik und Kinderpoliklinik im Dr von Haunerschen Kinderspital, Munich University Hospital, Munich, Germany
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  • T. Illig,

    1. Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Epidemiology, Neuherberg, Germany
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  • H.-E. Wichmann,

    1. Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Epidemiology, Neuherberg, Germany
    2. Department of Biometrics and Epidemiology, Ludwig-Maximilians University of Munich, Institute of Medical Data Management, Munich, Germany
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  • J. Heinrich,

    1. Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Epidemiology, Neuherberg, Germany
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  • the LISA and GINI Study Group

    1. Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Epidemiology, Neuherberg, Germany
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Dr Chih-Mei Chen
Institute of Epidemiology
Helmholtz Zentrum München
German Research Centre for Environmental Health
Ingolstaedter Landstrasse 1
D-85764 Neuherberg
Germany

Abstract

Background:  In a recent genome wide scan, a functional promoter variant (rs2251746) in the gene encoding the alpha chain of the high affinity receptor for immunoglobulin E (IgE) (FCER1A) was identified as major determinant of serum IgE levels.

Objective:  The aim of this study was to investigate the role of rs2251746 on total IgE levels measured at different stages of life from birth (cord blood) up to the age of 6 and to evaluate its interaction with the environmental influences in two German birth cohorts.

Method:  Data from two German birth cohorts were analysed (n = 1043 for the LISA cohort and n = 1842 for the GINI cohort). In the studies, total serum IgE was measured from cord blood, and blood samples taken at the age of 2/3 and 6 years. In a subgroup of the LISA study, house dust samples were collected at age of 3 months and the amount of endotoxin was determined. Random effect models were used to analyse the longitudinal health outcomes.

Results:  In the two cohorts, the heterozygote and the rare homozygote of rs2251746 was consistently associated with lower total IgE levels from birth up to the age of 6 years with an allele-dose effect (P < 0.02 for blood samples taken at each time point in both cohorts). No interaction between the two FCER1A encoding gene and environmental exposures including endotoxin, worm infestation and day care centre attendance during early childhood were observed.

Conclusion:  Common variants in FCER1A strongly influence basal IgE production independently from environmental stimuli. These effects can be observed already in cord blood pointing to altered gene expression in foetus.

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