CYP2C9*3 Loss-of-Function Allele Is Associated With Acute Upper Gastrointestinal Bleeding Related to the Use of NSAIDs Other Than Aspirin

Clin Pharmacol Ther. 2010 Jun;87(6):693-8. doi: 10.1038/clpt.2010.33. Epub 2010 May 5.


Nonsteroidal anti-inflammatory drugs (NSAIDs), other than aspirin, are to some extent metabolized by cytochrome P450 2C9 (CYP2C9). The CYP2C9 359Leu (CYP2C9*3) loss-of-function allele could be a risk factor for acute upper gastrointestinal bleeding (AUGIB) related to the use of NSAIDs other than aspirin. To test this hypothesis, we performed a prospective, multicenter, case-case study in patients hospitalized for AUGIB related to the use of NSAIDs. A total of 131 patients had been treated with aspirin and 57 patients had been treated with an NSAID other than aspirin (non-ASP). In the aspirin group, 12 patients (9.2%) had the CYP2C9 359Leu allele as compared with 19 (33.3%) in the non-ASP group (odds ratio (OR) = 5.0; 95% confidence interval 2.2-11.1, P < 0.0001). In a multivariate analysis, CYP2C9 359Leu remained associated with the non-ASP group (OR = 7.2 (2.6-20.3), P = 0.0002) even though 40% of these patients were under treatment with antiulcer drugs at the time of admission. Therefore the results of the study support the hypothesis that the CYP2C9 359Leu allele is a robust risk factor for AUGIB related to the use of NSAIDs other than aspirin.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism
  • Anti-Ulcer Agents / therapeutic use
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aspirin / adverse effects*
  • Case-Control Studies
  • Cytochrome P-450 CYP2C9
  • Female
  • Gastrointestinal Hemorrhage / chemically induced*
  • Gastrointestinal Hemorrhage / genetics
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prospective Studies
  • Risk Factors


  • Anti-Inflammatory Agents, Non-Steroidal
  • Anti-Ulcer Agents
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • Aspirin