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Genotype and risk of major bleeding during warfarin treatment.

AbstractAIM:
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.
AuthorsVivian 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
JournalPharmacogenomics (Pharmacogenomics) Vol. 15 Issue 16 Pg. 1973-83 (Dec 2014) ISSN: 1744-8042 [Electronic] England
PMID25521356 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Warfarin
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP2C9
  • Cytochrome P450 Family 4
  • CYP4F2 protein, human
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases
Topics
  • Adult
  • Aged
  • Biological Specimen Banks
  • Cytochrome P-450 CYP2C9 (genetics)
  • Cytochrome P-450 Enzyme System (genetics)
  • Cytochrome P450 Family 4
  • Dose-Response Relationship, Drug
  • Ethnicity
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Variation
  • Genotype
  • Hemorrhage (chemically induced, drug therapy, genetics)
  • Humans
  • Male
  • Middle Aged
  • Risk Factors
  • Vitamin K Epoxide Reductases (genetics)
  • Warfarin (administration & dosage, adverse effects)

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