The role of LTA4H and ALOX5AP polymorphism in asthma and allergy susceptibility.
The role of LTA4H and ALOX5AP polymorphism in asthma and allergy susceptibility.
Leukotrienes (LTs) have been identified as central mediators in asthma and allergy. Pharmacological inhibition of cysteinyl-LT activity improves asthma symptoms and control. Accumulating evidence suggests a role for the dihydroxy leukotriene LTB(4) in airway disease. LTA(4) hydrolase and 5-lipoxygenase activating protein have key roles in LTB(4) production. Single nucleotide polymorphism (SNPs) and haplotypes spanning the LTA4H and ALOX5AP genes have been associated with LTB(4) production and myocardial infarction (MI). Objective: To assess the contribution of LTA4H and ALOX5AP polymorphism to asthma and allergy susceptibility. Methods: Three hundred and forty-one Caucasian families (two asthmatic siblings) were genotyped for eight SNPs spanning ALOX5AP and five SNPs spanning LTA4H. Association analyses of asthma and related phenotypes (total IgE, atopy, bronchial hyper-responsiveness, FEV(1)) were undertaken using the Family Based Association Test. Results: Single point analyses identified association (P < 0.05) between SNPs SG13S114, SG13S89, SG13S41 (ALOX5AP), rs1978331 (LTA4H) and asthma and/or related phenotypes. Haplotype analyses using all LTA4H SNPs identified a single key risk haplotype for the development of asthma (P = 0.006) and related phenotypes (P = 0.042-0.005). Haplotype analyses using all ALOX5AP SNPs identified several asthma and atopy risk and protective haplotypes. There was limited correlation with previously identified MI risk haplotypes in both genes. Carriers of both ALOX5AP SG13S41 and LTA4H rs1978331 alleles had an increased risk of developing asthma (OR 2.17, CI 1.41-3.32). Conclusions: These data provide evidence for the role of SNPs spanning the ALOX5AP and LTA4H genes in asthma and atopy susceptibility in the Caucasian population and support a role for LTB(4) in disease pathogenesis.
allergy, asthma, leukotriene, polymorphism, susceptibility
1046-1053
Holloway, J.W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Barton, S.J
4f674382-ca0b-44ad-9670-e71a0b134ef0
Holgate, S.T .
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Rose-Zerilli, M.J.
5b58c2f6-62b2-4683-a777-cae95cdf1c62
Sayers, I.
230e01df-0685-438a-9173-df1aead72390
May 2008
Holloway, J.W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Barton, S.J
4f674382-ca0b-44ad-9670-e71a0b134ef0
Holgate, S.T .
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Rose-Zerilli, M.J.
5b58c2f6-62b2-4683-a777-cae95cdf1c62
Sayers, I.
230e01df-0685-438a-9173-df1aead72390
Holloway, J.W., Barton, S.J, Holgate, S.T ., Rose-Zerilli, M.J. and Sayers, I.
(2008)
The role of LTA4H and ALOX5AP polymorphism in asthma and allergy susceptibility.
Allergy, 59 (8), .
(doi:10.1111/j.1398-9995.2008.01667.x).
Abstract
Leukotrienes (LTs) have been identified as central mediators in asthma and allergy. Pharmacological inhibition of cysteinyl-LT activity improves asthma symptoms and control. Accumulating evidence suggests a role for the dihydroxy leukotriene LTB(4) in airway disease. LTA(4) hydrolase and 5-lipoxygenase activating protein have key roles in LTB(4) production. Single nucleotide polymorphism (SNPs) and haplotypes spanning the LTA4H and ALOX5AP genes have been associated with LTB(4) production and myocardial infarction (MI). Objective: To assess the contribution of LTA4H and ALOX5AP polymorphism to asthma and allergy susceptibility. Methods: Three hundred and forty-one Caucasian families (two asthmatic siblings) were genotyped for eight SNPs spanning ALOX5AP and five SNPs spanning LTA4H. Association analyses of asthma and related phenotypes (total IgE, atopy, bronchial hyper-responsiveness, FEV(1)) were undertaken using the Family Based Association Test. Results: Single point analyses identified association (P < 0.05) between SNPs SG13S114, SG13S89, SG13S41 (ALOX5AP), rs1978331 (LTA4H) and asthma and/or related phenotypes. Haplotype analyses using all LTA4H SNPs identified a single key risk haplotype for the development of asthma (P = 0.006) and related phenotypes (P = 0.042-0.005). Haplotype analyses using all ALOX5AP SNPs identified several asthma and atopy risk and protective haplotypes. There was limited correlation with previously identified MI risk haplotypes in both genes. Carriers of both ALOX5AP SG13S41 and LTA4H rs1978331 alleles had an increased risk of developing asthma (OR 2.17, CI 1.41-3.32). Conclusions: These data provide evidence for the role of SNPs spanning the ALOX5AP and LTA4H genes in asthma and atopy susceptibility in the Caucasian population and support a role for LTB(4) in disease pathogenesis.
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Published date: May 2008
Keywords:
allergy, asthma, leukotriene, polymorphism, susceptibility
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Local EPrints ID: 59328
URI: http://eprints.soton.ac.uk/id/eprint/59328
ISSN: 0105-4538
PURE UUID: 665c98f5-1fe6-45e4-9fd5-1a1d6aeb7984
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Date deposited: 03 Sep 2008
Last modified: 16 Mar 2024 03:22
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Author:
M.J. Rose-Zerilli
Author:
I. Sayers
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