Cyclooxygenase-2 (COX-2) polymorphisms and risk of inflammatory bowel disease in a Scottish and Danish case–control study

Vibeke Andersen , Elaine Nimmo, Henrik Bygum Krarup, Hazel Drummond, Jane Christensen, Gwo-tzer Ho, Mette Østergaard, Anja Ernst, Charles Lees, Bent Ascanius Jacobsen, Jack Satsangi, Ulla Vogel

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    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. (Inflamm Bowel Dis 2011)
    OriginalsprogEngelsk
    TidsskriftInflammatory Bowel Diseases
    Vol/bind17
    Udgave nummer4
    Sider (fra-til)937-946
    ISSN1078-0998
    DOI
    StatusUdgivet - 2011

    Citer dette

    Andersen , V., Nimmo, E., Krarup, H. B., Drummond, H., Christensen, J., Ho, G., Østergaard, M., Ernst, A., Lees, C., Jacobsen, B. A., Satsangi, J., & Vogel, U. (2011). Cyclooxygenase-2 (COX-2) polymorphisms and risk of inflammatory bowel disease in a Scottish and Danish case–control study. Inflammatory Bowel Diseases, 17(4), 937-946. https://doi.org/10.1002/ibd.21440