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

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Limdi NA, Arnett DK, Goldstein JA, Beasley TM, McGwin G, Adler BK, Acton RT

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

Pharmacogenomics. 2008 May;9(5):511-26. doi: 10.2217/14622416.9.5.511.

PubMed ID

18466099 [ View in PubMed

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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) 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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Dicoumarol	Cytochrome P450 2C9	Protein	Humans	Unknown	Substrate	Details