title: Cyclooxygenase-2 gene polymorphisms in an Australian population: association of the -1195G > A promoter polymorphism with mild asthma.
abstract: BACKGROUND
  Cyclooxygenase (COX)-2 is an inducible enzyme responsible for catalysing the formation of prostaglandins (PGs) in settings of inflammation. Single nucleotide polymorphisms (SNPs) of the COX-2 gene may influence gene transcription and PG production in the asthmatic airway.
  
  
  OBJECTIVE
  To evaluate the frequencies of COX-2 SNPs in an Australian Caucasian population, and determine potential associations between common COX-2 promoter SNPs and asthma, asthma severity and aspirin-intolerant asthma (AIA).
  
  
  METHODS
  The frequencies of 25 COX-2 SNPs were determined in a random population (n=176). The SNPs with a minor allele frequency of >10% were then studied in asthmatic (n=663), non-asthmatic controls (n=513) and AIA subjects (n=58). Genotype, allele and haplotype associations were assessed. Functional assessment of SNPs was performed by transfection into HeLa cells measured using the luciferase dual-reporter assay system.
  
  
  RESULTS
  Eighteen COX-2 SNPs were not detected, five were rare and two promoter SNPs, -1195G>A (rs689465), and -1290A>G (rs689466), were further studied. The A allele of the -1195 SNP was present at a significantly higher frequency among all asthmatic subjects (P=0.012). Over 60% of the asthmatic individuals were -1195A homozygotes compared with 54.6% of the control subjects (odds ratio, 1.35; 95% CI, 1.06-1.72, P=0.03). After classifying for severity, the mild asthmatics represented 64.6% of -1195AA individuals, the highest of all the asthma groups compared with 54.6% of the control subjects (odds ratio, 1.5; 95% CI, 1.12-2.02, P=0.02). The -1290A/-1195G/-765G haplotype was associated with a reduced incidence of asthma (odds ratio, 0.76; 95% CI, 0.61-0.95, P=0.017).
  
  
  CONCLUSIONS
  The -1195G>A polymorphism appears to be associated with asthma, and in particular with mild asthma.
authors.affiliation: Lung Institute of Western Australia and Centre for Asthma, Allergy and Respiratory Research, The University of Western Australia, Perth, WA, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Shi
authors.forename: N L
authors.initials: NL
authors.lastname: Misso
authors.forename: M-A
authors.initials: MA
authors.lastname: Kedda
authors.forename: J
authors.initials: J
authors.lastname: Horn
authors.forename: M D
authors.initials: MD
authors.lastname: Welch
authors.forename: D L
authors.initials: DL
authors.lastname: Duffy
authors.forename: C
authors.initials: C
authors.lastname: Williams
authors.forename: P J
authors.initials: PJ
authors.lastname: Thompson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000009:adverse effects; D001249:Asthma / Q000139:chemically induced / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D001315:Australia; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010957:Plasmids; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014162:Transfection; D044465:White People
chemical_list: D051546:Cyclooxygenase 2; D001241:Aspirin