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Polymorphisms in the 5-lipoxygenase activating protein (ALOX5AP) gene are not associated with asthma in an Australian population

Authors

  • M.-A. Kedda,

    1. The Co-operative Research Centre (CRC) for Asthma, the Asthma and Allergy Research Institute (Inc.), and the Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Perth, Australia,
    2. The Western Australian Institute for Medical Research and Centre for Medical Research, Perth, Australia
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  • P. Worsley,

    1. The Co-operative Research Centre (CRC) for Asthma, the Asthma and Allergy Research Institute (Inc.), and the Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Perth, Australia,
    2. The Western Australian Institute for Medical Research and Centre for Medical Research, Perth, Australia
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  • J. Shi,

    1. The Co-operative Research Centre (CRC) for Asthma, the Asthma and Allergy Research Institute (Inc.), and the Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Perth, Australia,
    2. The Western Australian Institute for Medical Research and Centre for Medical Research, Perth, Australia
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  • S. Phelps,

    1. The Co-operative Research Centre (CRC) for Asthma, the Asthma and Allergy Research Institute (Inc.), and the Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Perth, Australia,
    2. The Western Australian Institute for Medical Research and Centre for Medical Research, Perth, Australia
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  • D. Duffy,

    1. Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia
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  • P. J. Thompson

    1. The Co-operative Research Centre (CRC) for Asthma, the Asthma and Allergy Research Institute (Inc.), and the Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Perth, Australia,
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P. J. Thompsom, Asthma and Allergy Research Institute, Ground Floor E Block, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia.
E-mail: aari@aari.uwa.edu.au

Summary

Background The cysteinyl-leukotrienes (cys-LTs) are important pro-inflammatory mediators in asthma, and have been shown to have a role in specific disease subtypes, including asthma severity. Few studies have investigated the role of polymorphisms in the ALOX5AP gene, encoding 5-lipoxygenase activating protein (FLAP), and asthma. We hypothesized that polymorphisms in this gene are associated with asthma and in particular, with asthma severity, in an Australian population.

Objective To screen the coding region of the ALOX5AP gene for polymorphisms and to determine the association between previously described polymorphisms and asthma and asthma severity in an Australian population.

Methods We used PCR-SSCP and PCR-RFLP analysis to examine a previously described promoter polyA variable repeat polymorphism and two intronic polymorphisms (IVS2+12C>A, IVS2+105T>C), and to screen all five exons of the gene for new polymorphisms, in a large Australian population of randomly selected, non-asthmatic controls (n=457), mild asthmatics (n=274), moderate asthmatics (n=231) and severe asthmatics (n=79).

Results We confirmed the presence of two polymorphisms in intron 2 and found no association between these polymorphisms and asthma or asthma severity, nor between a promoter polymorphism in the ALOX5AP gene and asthma or asthma severity. Gene fragment analysis of the promoter polymorphism revealed novel, conserved repeat numbers in our population, and no new polymorphisms were found in the coding region of the gene.

Conclusion These findings in a large, well characterized asthma population, reveal that, while FLAP is an important enzyme in cys-LTs biosynthesis, polymorphisms in the ALOX5AP gene are not likely to be functionally associated with the asthma phenotype.

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