Alpha-tryptase gene variation is associated with levels of circulating IgE and lung function in asthma
Alpha-tryptase gene variation is associated with levels of circulating IgE and lung function in asthma
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 ?-tryptase, an allelic variant of the more extensively studied ?-tryptase, is absent in substantial numbers of the general population. The degree to which ?-tryptase expression may be associated with asthma has not been studied. We have investigated the ?-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 ?-tryptase alleles, using high resolution melting assays. Standards for the possible ?-/?-tryptase ratios were constructed by cloning ?-and ?-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, FEV1, and atopy and asthma severity scores) were undertaken using family based association tests (FBAT).
Results
Four consistent melting patterns for the ?-tryptase genotype were identified with alleles carrying null, one or two copies of the ?-tryptase allele. Possessing one copy of ?-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 ?-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.
asthma, gene copy number variation, IgE, mast cell, tryptase
822-830
Abdelmotelb, A.M.
47ec298b-4ec1-48e4-8a19-39f2235de4a5
Rose-Zerilli, M.J.
08b3afa4-dbc2-4c0d-a852-2a9f33431199
Barton, S.J.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Holgate, S.T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Walls, A.F.
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Holloway, J.W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
June 2014
Abdelmotelb, A.M.
47ec298b-4ec1-48e4-8a19-39f2235de4a5
Rose-Zerilli, M.J.
08b3afa4-dbc2-4c0d-a852-2a9f33431199
Barton, S.J.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Holgate, S.T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Walls, A.F.
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Holloway, J.W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Abdelmotelb, A.M., Rose-Zerilli, M.J., Barton, S.J., Holgate, S.T., Walls, A.F. and Holloway, J.W.
(2014)
Alpha-tryptase gene variation is associated with levels of circulating IgE and lung function in asthma.
Clinical & Experimental Allergy, 44 (6), .
(doi:10.1111/cea.12259).
(PMID:24372627)
Abstract
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 ?-tryptase, an allelic variant of the more extensively studied ?-tryptase, is absent in substantial numbers of the general population. The degree to which ?-tryptase expression may be associated with asthma has not been studied. We have investigated the ?-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 ?-tryptase alleles, using high resolution melting assays. Standards for the possible ?-/?-tryptase ratios were constructed by cloning ?-and ?-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, FEV1, and atopy and asthma severity scores) were undertaken using family based association tests (FBAT).
Results
Four consistent melting patterns for the ?-tryptase genotype were identified with alleles carrying null, one or two copies of the ?-tryptase allele. Possessing one copy of ?-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 ?-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.
Text
Abdelmotelb_et_al-2014-Clinical_&_Experimental_Allergy
- Version of Record
More information
Accepted/In Press date: 27 November 2013
e-pub ahead of print date: 23 December 2013
Published date: June 2014
Keywords:
asthma, gene copy number variation, IgE, mast cell, tryptase
Organisations:
Human Development & Health, Clinical & Experimental Sciences
Identifiers
Local EPrints ID: 360841
URI: http://eprints.soton.ac.uk/id/eprint/360841
ISSN: 0954-7894
PURE UUID: c1380e79-a72d-4d94-9588-29d86fd2d9dd
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Date deposited: 02 Jan 2014 14:32
Last modified: 15 Mar 2024 03:36
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Author:
A.M. Abdelmotelb
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