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

Publication: Research - peer-reviewJournal article – Annual report year: 2011

  • Author: Andersen, Vibeke

    Viborg Regional Hospital, Denmark, Medical Department

  • Author: Nimmo, Elaine

    University of Edinburgh

  • Author: Krarup, Henrik B.

    Aalborg University Hospital

  • Author: Drummond, Hazel

    University of Edinburgh

  • Author: Christensen, Jane

    Danish Cancer Society, Institute of Cancer Epidemiology

  • Author: Ho, Gwo-tzer

    University of Edinburgh

  • Author: Østergaard, Mette

    Viborg Regional Hospital, Denmark, Biochemical Department

  • Author: Ernst, Anja

    Aalborg University Hospital

  • Author: Lees, Charlie

    University of Edinburgh

  • Author: Jacobsen, Bent A.

    Aalborg University Hospital

  • Author: Satsangi, Jack

    University of Edinburgh

  • Author: Vogel, Ulla Birgitte

    National Food Institute, Technical University of Denmark

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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.
Original languageEnglish
JournalInflammatory Bowel Diseases
Publication date2011
Volume17
Issue4
Pages937-946
ISSN1078-0998
DOIs
StatePublished

Bibliographical note

Supported by the Lundbeck Foundation, the Danish Research Council, the Western Danish Research Forum for Health Science, the County of Viborg, the Danish Colitis-Crohn Association, the Harboe Foundation, the Familien Erichsen Mindefond, John M Klein og hustrus mindelegat, and Fonden til Lægevidenskabens fremme.

CitationsWeb of Science® Times Cited: 5

Keywords

  • Single nucleotide polymorphisms, Crohn's disease, Ulcerative colitis, Smoking status
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