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Alpha‐tryptase gene variation is associated with levels of circulating I g E and lung function in asthma
Author(s) -
Abdelmotelb A. M.,
RoseZerilli M. J.,
Barton S. J.,
Holgate S. T.,
Walls A. F.,
Holloway J. W.
Publication year - 2014
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12259
Subject(s) - tryptase , atopy , immunology , immunoglobulin e , allergen , asthma , allele , house dust mite , population , allergy , biology , medicine , gene , genetics , mast cell , antibody , environmental health
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 I g E , bronchial hyperresponsiveness to methacholine, forced expiratory volume in 1s ( FEV 1 ) 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 I g E levels and higher FEV 1 measurements, while two copies were related to higher serum concentrations of total and dust mite‐specific I g E and greater atopy severity scores. Conclusions and Clinical Relevance Associations of α‐tryptase copy number with serum I g E levels, atopy scores and bronchial function may reflect roles for tryptases in regulating I g E production and other processes in asthma.