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.
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: Hilbert S de Vries; Rene H M te Morsche; Martijn G H van Oijen; Iris D Nagtegaal; Wilbert H M Peters; Dirk J de Jong Journal: PLoS One Date: 2010-11-24 Impact factor: 3.240
Authors: Vibeke Andersen; Anja Ernst; Jurgita Sventoraityte; Limas Kupcinskas; Bent A Jacobsen; Henrik B Krarup; Ulla Vogel; Laimas Jonaitis; Goda Denapiene; Gediminas Kiudelis; Tobias Balschun; Andre Franke Journal: BMC Med Genet Date: 2011-10-13 Impact factor: 2.103
Authors: Timothy R Elliott; Neil B Rayment; Barry N Hudspith; Rebecca E Hands; Kirstin Taylor; Gareth C Parkes; Natalie J Prescott; Liljana Petrovska; John Hermon-Taylor; Jonathan Brostoff; Alex Boussioutas; Christopher G Mathew; Stephen A Bustin; Jeremy D Sanderson Journal: BMC Gastroenterol Date: 2015-07-03 Impact factor: 3.067