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:
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Authors | 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 |
Journal | Pharmacogenomics
(Pharmacogenomics)
Vol. 15
Issue 16
Pg. 1973-83
(Dec 2014)
ISSN: 1744-8042 [Electronic] England |
PMID | 25521356
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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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
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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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