Genotype and risk of major bleeding during warfarin treatment.

Kawai VK, Cunningham A, Vear SI, Van Driest SL, Oginni A, Xu H, Jiang M, Li C, Denny JC, Shaffer C, Bowton E, Gage BF, Ray WA, Roden DM, Stein CM
Pharmacogenomics. 2014 15 (16): 1973-83

PMID: 25521356 · PMCID: PMC4304738 · DOI:10.2217/pgs.14.153

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.

MeSH Terms (20)

Adult Aged Biological Specimen Banks Cytochrome P-450 CYP2C9 Cytochrome P-450 Enzyme System Cytochrome P450 Family 4 Dose-Response Relationship, Drug Ethnic Groups Female Gene Frequency Genetic Association Studies Genetic Variation Genotype Hemorrhage Humans Male Middle Aged Risk Factors Vitamin K Epoxide Reductases Warfarin

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