Genotype and risk of major bleeding during warfarin treatment

Vivian K. Kawai, Andrew Cunningham, Susan I. Vear, Sara L. Van Driest, Abimbola Oginni, Hua Xu, Min Jiang, Chun Li, Joshua C. Denny, Christian Shaffer, Erica Bowton, Brian F. Gage, Wayne A. Ray, Dan M. Roden, C. Michael Stein

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Aim: To determine whether genetic variants associated with warfarin dose variability were associated with increased risk of major bleeding during warfarin therapy. Materials & methods: Using Vanderbilt's DNA biobank we compared the prevalence of CYP2C9, VKORC1 and CYP4F2 variants in 250 cases with major bleeding and 259 controls during warfarin therapy. Results: CYP2C9∗3 was the only allele that differed significantly among cases (14.2%) and controls (7.8%; p = 0.022). In the 214 (85.6%) cases with a major bleed 30 or more days after warfarin initiation, CYP2C9∗3 was the only variant associated with bleeding (adjusted odds ratio: 2.05; 95% CI: 1.04, 4.04). Conclusion: The CYP2C9∗3 allele may double the risk of major bleeding among patients taking warfarin for 30 or more days.

Original languageEnglish
Pages (from-to)1973-1983
Number of pages11
JournalPharmacogenomics
Volume15
Issue number16
DOIs
StatePublished - Dec 1 2014

Keywords

  • CYP2C9
  • CYP4F2
  • VKORC1
  • pharmacogenetics
  • risk of major bleeding
  • warfarin

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