OIV-A-3Vitamin K epoxide reductase complex 1 polymorphism and warfarin dose in African Americans

Abstract

BACKGROUND/AIMS A polymorphism at position 6853 (G C) in the gene encoding vitamin K epoxide reductase complex 1 (VKORC1), the active site for warfarin, has been associated with warfarin dose requirements in Caucasians. We sought to determine whether the VKORC1 G6853C polymorphism is associated with warfarin dose requirements in African Americans. METHODS Genetic samples and information on vitamin K intake and warfarin adherence were collected from 75 African Americans on a stable dose of warfarin, defined as the same dose for ≥3 consecutive clinic visits. Demographic data and INR values were also collected. Patients taking drugs known to interact with warfarin were excluded from the study. Genotype was determined by PCR and RFLP methods. Warfarin dose requirements and characteristics were compared by genotype. RESULTS The genotype distribution was in Hardy Weinberg equilibrium. The frequencies of the GG, GC, and CC genotypes were 69%, 23%, and 8%, respectively. There were no significant differences in demographic characteristics, INR, vitamin K intake, or warfarin adherence among genotype groups. Median warfarin dose was similar in heterozygotes[6.0 (range 2.7–13.6) mg/day] and G allele homozygotes[6.6 (3.1–14.3) mg/day]. However, median warfarin dose requirements were lower in C allele homozygotes[3.8 (2.0–7.5) mg/day] compared to G allele carriers; p=0.02. CONCLUSIONS Our data suggest that African Americans with the VKORC1 6853 CC genotype require lower warfarin doses. Clinical Pharmacology & Therapeutics (2005) 79, P32–P32; doi: 10.1016/j.clpt.2005.12.116