TY - JOUR

T1 - Cyclooxygenase-2 (COX-2) Polymorphisms and Risk of Inflammatory Bowel Disease in a Scottish and Danish Case–Control Study

A1 - Andersen,Vibeke

A1 - Nimmo,Elaine

A1 - Krarup,Henrik B.

A1 - Drummond,Hazel

A1 - Christensen,Jane

A1 - Ho,Gwo-tzer

A1 - Østergaard,Mette

A1 - Ernst,Anja

A1 - Lees,Charlie

A1 - Jacobsen,Bent A.

A1 - Satsangi,Jack

A1 - Vogel,Ulla Birgitte

AU - Andersen,Vibeke

AU - Nimmo,Elaine

AU - Krarup,Henrik B.

AU - Drummond,Hazel

AU - Christensen,Jane

AU - Ho,Gwo-tzer

AU - Østergaard,Mette

AU - Ernst,Anja

AU - Lees,Charlie

AU - Jacobsen,Bent A.

AU - Satsangi,Jack

AU - Vogel,Ulla Birgitte

PB - John/Wiley & Sons, Inc.

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - Single nucleotide polymorphisms

KW - Crohn's disease

KW - Ulcerative colitis

KW - Smoking status

U2 - 10.1002/ibd.21440

DO - 10.1002/ibd.21440

JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

SN - 1078-0998

IS - 4

VL - 17

SP - 937

EP - 946

ER -