Influence of CYP2C9 and VKORC1 on Warfarin Dose, Anticoagulation Attainment and Maintenance Among European–Americans and African–Americans

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Abstract
Aims: The influence of CYP2C9 and VKORC1 on warfarin dose, time to target International Normalized Ratio (INR), time to stabilization, and risk of over-anticoagulation (INR: >4) was assessed after adjustment for clinical factors, intraindividual variation in environmental factors and unobserved heterogeneity. Materials & Methods: Common CYP2C9 and VKORC1 polymorphisms were assessed in 302 European–Americans and 273 African–Americans receiving warfarin. Race-stratified multivariable analyses evaluated the influence of CYP2C9 and VKORC1 on warfarin response. Results & Conclusion: CYP2C9 and VKORC1 accounted for up to 30% of the variability in warfarin dose among European–Americans and 10% among African–Americans. Neither CYP2C9 nor VKORC1 influenced the time to target INR or stabilization among patients of either race, and neither influenced the risk of over-anticoagulation among African–Americans. The risk of over-anticoagulation was higher among European–Americans with variant VKORC1 1173C/T (p < 0.01) an...
Funding Information
  • National Institute of Neurological Disorders and Stroke (K23NS45598–01)
  • National Institute of Environmental Health Sciences
  • National Institutes of Health
  • Institute Center for Genotyping and Analysis (U54 RR020278–01)