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

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), 1103-1110. (doi:10.1046/j.1365-2222.2003.01733.x).

Abstract

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.

This record has no associated files available for download.

Contributors

Author: S. Barton

Author: J.W. Holloway

Author: A.P. Sampson

Download statistics