Influence of CYP2C9 and VKORC1 on warfarin dose, anticoagulation attainment and maintenance among European-Americans and African-Americans.

Academic Article

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) and marginally significant among those with variant CYP2C9 (p = 0.08) genotype. Although CYP2C9 and VKORC1 genotyping can facilitate individualized initiation of warfarin dose in African and European-Americans, the ability to predict the risk of over-anticoagulation is inconsistent across race. Identification of other factors that can predict such risk consistently in a racially diverse group will facilitate individualized maintenance of warfarin therapy.
  • Published In

  • Pharmacogenomics  Journal
  • Keywords

  • Adult, African Americans, Aged, Anticoagulants, Aryl Hydrocarbon Hydroxylases, Cohort Studies, Cytochrome P-450 CYP2C9, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, International Normalized Ratio, Male, Middle Aged, Mixed Function Oxygenases, Prospective Studies, Vitamin K Epoxide Reductases, Warfarin
  • Digital Object Identifier (doi)

    Author List

  • Limdi NA; Arnett DK; Goldstein JA; Beasley TM; McGwin G; Adler BK; Acton RT
  • Start Page

  • 511
  • End Page

  • 526
  • Volume

  • 9
  • Issue

  • 5