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

Nita A. Limdi, Donna K. Arnett, Joyce A. Goldstein, T. Mark Beasley, Gerald McGwin, Brian K. Adler, Ronald T. Acton

Research output: Contribution to journalArticlepeer-review

132 Scopus citations

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.

Original languageEnglish
Pages (from-to)511-526
Number of pages16
JournalPharmacogenomics
Volume9
Issue number5
DOIs
StatePublished - May 2008

Keywords

  • African-American
  • CYP2C9
  • Cohort study
  • European-American
  • Over-anticoagulation
  • Pharmacogenetics
  • VKORC1
  • Warfarin

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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