Polymorphisms in interleukin-1 receptor-associated kinase 4 are associated with total serum IgE

Authors

  • M. A. Tewfik,

    1. Department of Otolaryngology – Head and Neck Surgery, Montreal General Hospital, McGill University, Montreal, Canada
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  • Y. Bossé,

    1. McGill University and Genome Quebec Innovation Centre, Montreal, Canada
    2. Centre de Recherche, Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l’Université Laval, Québec, Canada
    3. Laval University Hospital Research Center (CRCHUL), Quebec, Canada
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  • M. Lemire,

    1. McGill University and Genome Quebec Innovation Centre, Montreal, Canada
    2. Ontario Institute for Cancer Research, Toronto, Ontario, Canada
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  • T. J. Hudson,

    1. McGill University and Genome Quebec Innovation Centre, Montreal, Canada
    2. Ontario Institute for Cancer Research, Toronto, Ontario, Canada
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  • S. Vallée-Smejda,

    1. Département d’Otorhinolaryngologie, Hôpital Hôtel-Dieu, Université de Montréal, Montreal, Canada
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  • H. Al-Shemari,

    1. Department of Otolaryngology – Head and Neck Surgery, Montreal General Hospital, McGill University, Montreal, Canada
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  • C. Laprise,

    1. Community Genomic Medicine Centre, University of Montréal, Chicoutimi University Hospital, Chicoutimi, Canada
    2. Université du Québec à Chicoutimi, Chicoutimi, Canada
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  • M. Desrosiers

    1. Department of Otolaryngology – Head and Neck Surgery, Montreal General Hospital, McGill University, Montreal, Canada
    2. Département d’Otorhinolaryngologie, Hôpital Hôtel-Dieu, Université de Montréal, Montreal, Canada
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Dr Martin Desrosiers
Montreal General Hospital
Rm. A2-141
1650 Cedar Avenue
Montreal
QC
Canada H3G 1A4

Abstract

Background:  Serum immunoglobulin E (IgE) level is recognized to be under strong genetic control, but the causal and susceptibility genes remain to be identified. We sought to investigate the association between single nucleotide polymorphisms (SNPs) in the Toll-like receptor (TLR) signaling pathway and total serum IgE level.

Methods:  A population of 206 patients with severe chronic rhinosinusitis (CRS) was used. Precise phenotyping of patients was accomplished by means of a questionnaire and clinical examination. Blood was drawn for measurement of total serum IgE, as well as DNA extraction. A maximally informative set of SNPs in the TLR1, 2, 3, 4, 6, 9, 10, CD14, MD2, MyD88, IRAK4, and TRAF6 genes were selected and genotyped. Significant findings were replicated in a second independent population of 956 subjects from 227 families with asthma.

Results:  A total of 97 out of 104 SNPs were successfully genotyped. Three SNPs in IRAK4– rs1461567, rs4251513, and rs4251559 – were associated with total serum IgE levels (P < 0.004). In the replication sample, the same SNPs as well as the same orientation of the risk allele were associated with IgE levels (P < 0.031).

Conclusions:  These results demonstrate a clear association between polymorphisms in the IRAK4 gene and serum IgE levels in patients with CRS and asthma. IRAK4 may be important in the regulation of IgE levels in patients with inflammatory diseases of the airways.

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