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

    Resumé

    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

    Emneord

      Citer dette

      Andersen , V., Nimmo, E., Krarup, H. B., Drummond, H., Christensen, J., Ho, G., ... 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
      Andersen , Vibeke ; Nimmo, Elaine ; Krarup, Henrik Bygum ; Drummond, Hazel ; Christensen, Jane ; Ho, Gwo-tzer ; Østergaard, Mette ; Ernst, Anja ; Lees, Charles ; Jacobsen, Bent Ascanius ; Satsangi, Jack ; Vogel, Ulla. / Cyclooxygenase-2 (COX-2) polymorphisms and risk of inflammatory bowel disease in a Scottish and Danish case–control study. I: Inflammatory Bowel Diseases. 2011 ; Bind 17, Nr. 4. s. 937-946.
      @article{b0e849ad94034633a948009fb5e0bddd,
      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. (Inflamm Bowel Dis 2011)",
      keywords = "Crohn's disease, single nucleotide polymorphisms, smoking status, ulcerative colitis",
      author = "Vibeke Andersen and Elaine Nimmo and Krarup, {Henrik Bygum} and Hazel Drummond and Jane Christensen and Gwo-tzer Ho and Mette {\O}stergaard and Anja Ernst and Charles Lees and Jacobsen, {Bent Ascanius} and Jack Satsangi and Ulla Vogel",
      year = "2011",
      doi = "10.1002/ibd.21440",
      language = "English",
      volume = "17",
      pages = "937--946",
      journal = "Inflammatory Bowel Diseases",
      issn = "1078-0998",
      publisher = "Lippincott Williams & Wilkins",
      number = "4",

      }

      Andersen , V, Nimmo, E, Krarup, HB, Drummond, H, Christensen, J, Ho, G, Østergaard, M, Ernst, A, Lees, C, Jacobsen, BA, 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, bind 17, nr. 4, s. 937-946. https://doi.org/10.1002/ibd.21440

      Cyclooxygenase-2 (COX-2) polymorphisms and risk of inflammatory bowel disease in a Scottish and Danish case–control study. / Andersen , Vibeke ; Nimmo, Elaine; Krarup, Henrik Bygum; Drummond, Hazel; Christensen, Jane; Ho, Gwo-tzer; Østergaard, Mette; Ernst, Anja; Lees, Charles; Jacobsen, Bent Ascanius; Satsangi, Jack; Vogel, Ulla.

      I: Inflammatory Bowel Diseases, Bind 17, Nr. 4, 2011, s. 937-946.

      Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

      TY - JOUR

      T1 - Cyclooxygenase-2 (COX-2) polymorphisms and risk of inflammatory bowel disease in a Scottish and Danish case–control study

      AU - Andersen , Vibeke

      AU - Nimmo, Elaine

      AU - Krarup, Henrik Bygum

      AU - Drummond, Hazel

      AU - Christensen, Jane

      AU - Ho, Gwo-tzer

      AU - Østergaard, Mette

      AU - Ernst, Anja

      AU - Lees, Charles

      AU - Jacobsen, Bent Ascanius

      AU - Satsangi, Jack

      AU - Vogel, Ulla

      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. (Inflamm Bowel Dis 2011)

      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. (Inflamm Bowel Dis 2011)

      KW - Crohn's disease

      KW - single nucleotide polymorphisms

      KW - smoking status

      KW - ulcerative colitis

      U2 - 10.1002/ibd.21440

      DO - 10.1002/ibd.21440

      M3 - Journal article

      VL - 17

      SP - 937

      EP - 946

      JO - Inflammatory Bowel Diseases

      JF - Inflammatory Bowel Diseases

      SN - 1078-0998

      IS - 4

      ER -