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 language | English |
---|---|
Pages (from-to) | 511-526 |
Number of pages | 16 |
Journal | Pharmacogenomics |
Volume | 9 |
Issue number | 5 |
DOIs | |
State | Published - May 2008 |
Keywords
- African-American
- CYP2C9
- Cohort study
- European-American
- Over-anticoagulation
- Pharmacogenetics
- VKORC1
- Warfarin
ASJC Scopus subject areas
- Molecular Medicine
- Genetics
- Pharmacology