A functional polymorphism in the promoter region of the cyclooxygenase-2 gene is not associated with asthma and atopy in an Australian population

Authors

  • J. Shi,

    1. Asthma and Allergy Research Institute (Inc.) and Centre for Asthma, Allergy and Respiratory Research,
    2. Cooperative Research Centre for Asthma,
    3. Western Australian Institute for Medical Research and Centre for Medical Research, The University of Western Australia, Perth, Australia
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  • N. L. Misso,

    1. Asthma and Allergy Research Institute (Inc.) and Centre for Asthma, Allergy and Respiratory Research,
    2. Cooperative Research Centre for Asthma,
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  • D. L. Duffy,

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

    1. Asthma and Allergy Research Institute (Inc.) and Centre for Asthma, Allergy and Respiratory Research,
    2. Cooperative Research Centre for Asthma,
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  • M.-A. Kedda

    1. Asthma and Allergy Research Institute (Inc.) and Centre for Asthma, Allergy and Respiratory Research,
    2. Cooperative Research Centre for Asthma,
    3. Western Australian Institute for Medical Research and Centre for Medical Research, The University of Western Australia, Perth, Australia
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A/Prof. Philip J. Thompson, Asthma and Allergy Research Institute, Ground Floor, E Block, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia. E-mail: pjthomps@aari.uwa.edu.au

Summary

Background Cyclooxygenase (COX)-2 is a key inducible enzyme that regulates the production of anti-inflammatory prostaglandin E2. A single-nucleotide polymorphism, −765G>C, located within a stimulatory protein-1 binding site in the COX-2 promoter region, has been shown to have significantly lower promoter activity in vitro compared with the wild-type and was associated with decreased plasma levels of C-reactive protein after coronary artery bypass surgery. We hypothesized that this polymorphism, which may result in decreased COX-2 transcription, could be associated with more severe asthma, and/or aspirin-intolerant asthma (AIA).

Objective To determine the association between the −765G>C COX-2 polymorphism and asthma, disease severity and AIA in a large, well-phenotyped Australian population.

Methods PCR and restriction fragment length polymorphism analysis was used to characterize the polymorphism in an Australian Caucasian population of patients with mild (n=322), moderate (n=254) or severe (n=88) asthma and in non-asthmatic control subjects (n=512), as well as in patients with AIA (n=58). Genotype and allele association analyses were performed using χ2 tests.

Results The polymorphic −765C allele was present in approximately 30% of asthmatic patients and non-asthmatic controls. There was no association between the −765G>C polymorphism and asthma (P=0.920), disease severity (P=0.840), atopy (P=0.655) or AIA (P=0.841) in this population.

Conclusion Although the −765G>C polymorphism may have lower promoter activity and result in decreased COX-2 expression, it is not associated with asthma, disease severity, AIA or atopy in this Australian population.

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