title: A functional polymorphism in the promoter region of the cyclooxygenase-2 gene is not associated with asthma and atopy in an Australian population.
abstract: BACKGROUND
  Cyclooxygenase (COX)-2 is a key inducible enzyme that regulates the production of anti-inflammatory prostaglandin E(2). 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 chi(2) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Asthma and Allergy Research Institute (Inc.) and Centre for Asthma, Allergy and Respiratory Research, The University of Western Australia, Perth, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Shi
authors.forename: N L
authors.initials: NL
authors.lastname: Misso
authors.forename: D L
authors.initials: DL
authors.lastname: Duffy
authors.forename: P J
authors.initials: PJ
authors.lastname: Thompson
authors.forename: M-A
authors.initials: MA
authors.lastname: Kedda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D001241:Aspirin / Q000009:adverse effects; D001249:Asthma / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics*; D051546:Cyclooxygenase 2; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000201:enzymology / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin