INTRODUCTION: African-Americans are under-represented in studies assessing 
contributors to warfarin response. Our primary objective was to determine 
whether the genes for cytochrome P450 (CYP) 2C9, nicotinamide adenine 
dinucleotide phosphate, reduced, quinone oxidoreductase (NQO1) and vitamin K 
epoxide reductase complex subunit 1 (VKORC1) are associated with warfarin dose 
requirements in African-Americans.
PATIENTS AND METHODS: The following factors were assessed: demographics; 
clinical data; the CYP2C9 Arg144Cys (*2), Ile358Leu (*3) and Asp360Glu (*5); 
NQO1 Pro187Ser (*1/*2); and VKORC1 G6853C genotypes were analyzed in 115 
African-Americans on stable warfarin doses.
RESULTS: Allele frequencies were 0.05 for the CYP2C9 *2, *3 or *5 alleles; 0.20 
for NQO1 *2; and 0.25 for VKORC1 6853C. Possession of a CYP2C9*2, *3 or *5 
allele was associated with a 38% lower warfarin dose compared with the *1/*1 
genotype (30 +/- 13 vs 48 +/- 18 mg/week; p = 0.003). Neither the NQO1 *1/*2 nor 
VKORC1 G6853C genotype was associated with warfarin dose requirements in the 
population as a whole or in CYP2C9*1 allele homozygotes. Multiple regression 
analysis revealed that CYP2C9 genotype (p = 0.015), age (p < 0.001) and body 
surface area (p < 0.001) were jointly associated with warfarin dose 
requirements, and together explained 33% of the variability in warfarin dose 
requirements among African-Americans.
DISCUSSION: Our data suggest that CYP2C9 genotype, age and body size are 
important determinants of warfarin dose requirements in African-Americans. Our 
data further suggest that the VKORC1 G6853C polymorphism alone may not be useful 
for predicting warfarin dose requirements in this racial group.