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Promoter polymorphism in the 5-lipoxygenase (ALOX5) and 5-lipoxygenase-activating protein (ALOX5AP) genes and asthma susceptibility in a Caucasian population

Record type: Article

Background: 5-Lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP) are essential for cysteinyl-leukotriene (cys-LT) production, critical mediators in asthma.
Objective: We sought to identify novel promoter polymorphisms within the FLAP (ALOX5AP) gene promoter and test the role of these and the previously identified 5-LO (ALOX5) Sp1 promoter polymorphism in asthma susceptibility.
Methods: To assess genetic association with asthma phenotypes, we genotyped 341 Caucasian families (containing two asthmatic siblings) and non-asthmatic control subjects (n=184). Genetic association was determined by case–control and transmission disequilibrium test (TDT) analyses. To determine the functional role of polymorphisms on basal transcription, we generated ALOX5AP-promoter-luciferase constructs and transiently transfected human HeLa cells.
Results: A novel G/A substitution at –336 bp and a poly(A) repeat (n=19 or 23) at position ?169 to ?146 bp were identified in the ALOX5AP promoter. Genotyping found the ?336 A and poly(A19) alleles at frequencies of q=0.06 and 0.12, respectively. No ALOX5AP allele was associated with asthma or asthma-related phenotypes in case–control or TDT analyses. ALOX5AP-promoter-luciferase analyses did not support a functional role of the ?336 or poly(A) polymorphism in determining basal transcription. The ALOX5 Sp1 polymorphism was predominantly homozygous wild-type 5/5 (frequency q=0.70) and heterozygous 4/5 (q=0.23) genotypes and no allele was associated with asthma or asthma-related phenotypes.
Conclusion: Taken together, these data do not support a significant role for these polymorphisms in genetic susceptibility to asthma in the Caucasian population.

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Citation

Sayers, I., Barton, S., Rorke, S., Sawyer, J., Peng, Q., Beghe, B., Ye, S., Keith, T., Clough, J.B., Holloway, J.W., Sampson, A.P. and Holgate, S.T. (2003) Promoter polymorphism in the 5-lipoxygenase (ALOX5) and 5-lipoxygenase-activating protein (ALOX5AP) genes and asthma susceptibility in a Caucasian population Clinical & Experimental Allergy, 33, (8), pp. 1103-1110. (doi:10.1046/j.1365-2222.2003.01733.x).

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Published date: 2003

Identifiers

Local EPrints ID: 24938
URI: http://eprints.soton.ac.uk/id/eprint/24938
ISSN: 0954-7894
PURE UUID: 19030410-930d-4e13-a6c6-e79b2017f52e
ORCID for S. Barton: ORCID iD orcid.org/0000-0003-4963-4242
ORCID for J.W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 06 Apr 2006
Last modified: 17 Jul 2017 16:12

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Contributors

Author: I. Sayers
Author: S. Barton ORCID iD
Author: S. Rorke
Author: J. Sawyer
Author: Q. Peng
Author: B. Beghe
Author: S. Ye
Author: T. Keith
Author: J.B. Clough
Author: J.W. Holloway ORCID iD
Author: A.P. Sampson
Author: S.T. Holgate

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