Alpha-tryptase gene variation is associated with levels of circulating IgE and lung function in asthma

Authors

  • A. M. Abdelmotelb,

    1. Clinical and Experimental Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK
    2. Faculty of Medicine, Tanta University, Tanta, Egypt
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  • M. J. Rose-Zerilli,

    1. Human Development and Health Unit, Faculty of Medicine, University of Southampton, Southampton, UK
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  • S. J. Barton,

    1. MRC Life Course Epidemiology Unit, Faculty of Medicine, University of Southampton, Southampton, UK
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  • S. T. Holgate,

    1. Clinical and Experimental Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK
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  • A. F. Walls,

    Corresponding author
    1. Clinical and Experimental Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK
    • Correspondence:

      Dr Andrew F. Walls, Immunopharmacology Group, Clinical and Experimental Sciences, University of Southampton, Mailpoint 837, Level F, Sir Henry Wellcome Laboratories, Southampton General Hospital, Southampton SO16 6YD, UK.

      E-mail: afw1@soton.ac.uk

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  • J. W. Holloway

    1. Clinical and Experimental Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK
    2. Human Development and Health Unit, Faculty of Medicine, University of Southampton, Southampton, UK
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Summary

Background

Tryptase, a major secretory product of human mast cells has been implicated as a key mediator of allergic inflammation. Genetic variation in the tryptases is extensive, and α-tryptase, an allelic variant of the more extensively studied β-tryptase, is absent in substantial numbers of the general population. The degree to which α-tryptase expression may be associated with asthma has not been studied. We have investigated the α-tryptase gene copy number variation and its potential associations with phenotypes of asthma.

Objectives

Caucasian families (n = 341) with at least two asthmatic siblings (n = 1350) were genotyped for the α-tryptase alleles, using high-resolution melting assays. Standards for the possible α-/β-tryptase ratios were constructed by cloning α-and β-tryptase PCR products to generate artificial templates. Association analysis of asthma affection status and related phenotypes [total and allergen-specific serum IgE, bronchial hyperresponsiveness to methacholine, forced expiratory volume in 1s (FEV1) and atopy and asthma severity scores] was undertaken using family-based association tests (FBAT).

Results

Four consistent melting patterns for the α-tryptase genotype were identified with alleles carrying null, one or two copies of the α-tryptase allele. Possessing one copy of α-tryptase was significantly associated with lower serum levels of total and dust mite-specific IgE levels and higher FEV1 measurements, while two copies were related to higher serum concentrations of total and dust mite-specific IgE and greater atopy severity scores.

Conclusions and Clinical Relevance

Associations of α-tryptase copy number with serum IgE levels, atopy scores and bronchial function may reflect roles for tryptases in regulating IgE production and other processes in asthma.

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