title: Cyclooxygenase-2 (COX-2) polymorphisms and risk of inflammatory bowel disease in a Scottish and Danish case-control study.
abstract: BACKGROUND
  Inflammatory bowel diseases (IBDs) are a result of interactions between luminal pathogens and the intestinal immune response. Cyclooxygenase-2 (COX-2) plays a key role in the regulation of the inflammatory response upon stimulation by luminal pathogens via Toll-like receptors.
  
  
  METHODS
  Genotypes of the COX-2/PTGS2/PGHS2 A-1195G (rs689466), G-765C (rs20417), and T8473C (rs5275) polymorphisms were assessed in a Scottish and Danish case-control study including 732 Crohn's disease (CD) cases, 973 ulcerative colitis (UC) cases, and 1157 healthy controls using logistic regression.
  
  
  RESULTS
  Carriers of the COX-2 A-1195G variant allele had increased risk of UC (odds ratio [OR], 95% confidence interval [CI] = 1.25 [1.02-1.54], P = 0.03) and of both UC and IBD among never smokers (OR [95% CI] = 1.47 [1.11-1.96], P = 0.01 and OR [95% CI] = 1.37 [1.06-1.77], P = 0.02, respectively). Furthermore, this variant genotype was associated with increased risk of diagnosis of UC before age 40 years and with extensive UC (OR [95% CI] = 1.34 [1.11-1.62], P = 0.002 and OR [95% CI] = 1.32 [1.03-1.69], P = 0.03, respectively).
  
  
  CONCLUSIONS
  COX-2 A-1195G polymorphism was associated with the risk of UC, especially among never-smokers, suggesting that low activity of COX-2 may predispose to UC. Our results suggest that inclusion of smoking status may be essential for the evaluation of the role of genetic predisposition to IBD.
authors.affiliation: Medical Department, Viborg Regional Hospital, Viborg, Denmark. va9791@gmail.com
authors.forename: Vibeke
authors.initials: V
authors.lastname: Andersen
authors.forename: Elaine
authors.initials: E
authors.lastname: Nimmo
authors.forename: Henrik B
authors.initials: HB
authors.lastname: Krarup
authors.forename: Hazel
authors.initials: H
authors.lastname: Drummond
authors.forename: Jane
authors.initials: J
authors.lastname: Christensen
authors.forename: Gwo-Tzer
authors.initials: GT
authors.lastname: Ho
authors.forename: Mette
authors.initials: M
authors.lastname: Ostergaard
authors.forename: Anja
authors.initials: A
authors.lastname: Ernst
authors.forename: Charlie
authors.initials: C
authors.lastname: Lees
authors.forename: Bent A
authors.initials: BA
authors.lastname: Jacobsen
authors.forename: Jack
authors.initials: J
authors.lastname: Satsangi
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D003718:Denmark; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012606:Scotland; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004247:DNA; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human