Clinical & Experimental Allergy

Polymorphisms in the IRF-4 gene, asthma and recurrent bronchitis in children

Authors

  • L. A. Pinto,

    1. Biomedical Research Institute, Pontificia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
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    • These authors contributed equally to this study.
  • S. Michel,

    1. Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany
    2. Department of Pediatric Pneumology and Allergy, University Children`s Hospital Regensburg (KUNO), Regensburg, Germany
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    • These authors contributed equally to this study.
  • N. Klopp,

    1. Hannover Unified Biobank, Hannover Medical School, Hannover, Germany
    2. Research Unit of Molecular Epidemiology, Helmholtz Center Munich, Neuherberg, Germany
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  • C. Vogelberg,

    1. University Children's Hospital, Technical University Dresden, Dresden, Germany
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  • A. von Berg,

    1. Research Institute for the Prevention of Allergic Diseases, Children's Department, Marien-Hospital, Wesel, Germany
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  • A. Bufe,

    1. Department of Experimental Pneumology, Ruhr-University, Bochum, Germany
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  • A. Heinzmann,

    1. University Children's Hospital, Albert Ludwigs University, Freiburg, Germany
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  • O. Laub,

    1. Kinder- und Jugendarztpraxis Laub, Rosenheim, Germany
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  • B. Simma,

    1. Children's Department, University Teaching Hospital, Landeskrankenhaus Feldkirch, Feldkirch, Austria
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  • T. Frischer,

    1. University Children's Hospital Vienna, Vienna, Austria
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  • J. Genuneit,

    1. Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany
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  • M. Gorski,

    1. Genetic Epidemiology, Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany
    2. Department of Internal Medicine II (Nephrology), University Medical Center Regensburg, Regensburg, Germany
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  • T. Illig,

    1. Hannover Unified Biobank, Hannover Medical School, Hannover, Germany
    2. Research Unit of Molecular Epidemiology, Helmholtz Center Munich, Neuherberg, Germany
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  • M. Kabesch

    Corresponding author
    1. Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany
    2. Department of Pediatric Pneumology and Allergy, University Children`s Hospital Regensburg (KUNO), Regensburg, Germany
    3. Member of the German Lung Research Center (DLZ), Germany
    • Biomedical Research Institute, Pontificia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
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Correspondence:

Michael Kabesch, University Children's Hospital Regensburg (KUNO), Department of Pediatric Pneumology and Allergy, Campus St. Hedwig, Steinmetzstr. 1-3, D-93049 Regensburg, Germany.

E-mail: michael.kabesch@ukr.de

Summary

Background

Interferon-regulatory factors (IRFs) play a crucial role in immunity, not only influencing interferon expression but also T cell differentiation. IRF-4 was only recently recognized as a further major player in T cell differentiation.

Objective

As IRF-1 polymorphisms were shown to be associated with atopy and allergy, we comprehensively investigated effects of IRF-4 variants on allergy, asthma and related phenotypes in German children.

Methods

Fifteen tagging single nucleotide polymorphisms (SNPs) in the IRF-4 gene were genotyped by MALDI-TOF MS in the cross-sectional ISAAC phase II study population from Munich and Dresden (age 9–11; = 3099). Replication was performed in our previously established genome-wide association study (GWAS) data set (= 1303) consisting of asthma cases from the Multicenter Asthma Genetic in Childhood (MAGIC) study and reference children from the ISAAC II study.

Results

SNPs were not significantly associated with asthma but with bronchial hyperresponsiveness, atopy and, most interestingly, with recurrent bronchitis in the first data set. The IRF-4 variant rs9378805 was associated with recurrent bronchitis in the ISAAC population and replicated in the GWAS data set where further SNPs showed associations with recurrent bronchitis and asthma.

Conclusions

We found genetic associations in IRF-4 to be associated with recurrent bronchitis in our two study populations. Associated polymorphisms are localized in a putative regulatory element in the 3′UTR region of IRF-4. These findings suggest a putative role of IRF-4 in the development of bronchitis.

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