Influence of CYP2C9 Genotype on Warfarin Dose Among African–Americans and European–Americans

Abstract
Background: Cytochrome P450 (CYP)2C9 plays a vital role in drug metabolism. There has been an increased effort to identify polymorphisms within the gene and to determine their clinical consequences. However, most of these efforts have focused on populations of European descent. Herein we report the influence of CYP2C9 genotype on warfarin dose among European–American and African–American patients. We also identify two new mutations, one in the coding region and one in the noncoding region of the CYP2C9 gene. Methods: Patients (aged >20 years) were enrolled after obtaining medical, lifestyle and concomitant medication history. Changes in international normalized ratio, warfarin dose, co-medications, diet, physical activity and the occurrence of complications were documented. CYP2C9 genotype was determined using PCR with restriction fragment length polymorphisms, and pyrosequencing. Differences in genotype frequencies and Hardy–Weinberg equilibrium assumptions were assessed using χ2 statistics and exact tes...