Cytochrome P450 polymorphisms are associated with reduced warfarin dose

Background. Warfarin use is complicated by an erratic dose response. Interp atient variability associated with warfarin therapy may be partly attributa ble to polymorphisms of the cytochrome P450 (CYP) complex. The purpose of t his study was to ascertain the frequency and influence of CYP polymorphisms on warfarin dosing in our patient population. Methods. Patients receiving warfarin therapy were recruited from the inpati ent divisions of our hospital. Genotyping fm known polymorphic alleles of t he CYP subfamilies CYP2C9 (CYP2C9*1, CYP2C9*2, and CYD2C9*3) and CYP2A6 (CY P2A6*1, CYP2A6*2) with the use of standard methods of polymerase chain reac tion amplification was performed. An unpaired t test was used to statistica lly compare genotypes. Results. Genotype frequency in 38 patients is as follows: CYP2C9*1/CYP2C9*1 , 71%; CYP2C9*1/CYP2C9*2, 21%; CYP2C9*2/CYP2C9*2, 3%; CYP2C9*1/CYP2C9*3, 5% ; CYP2A6*1/CYP2A6*1, 95%; CYP2A6*1/CYP2A6*2, 5%. Compared to a wild-type ge notype, the presence of the CYP2C9*2, CYP2C9*3, or CYP2A6*2 allele was asso ciated with a significant reduction in weekly warfarin dose (mean weekly wa rfarin dose [+/- SE] for wild-type genotype was 0.397 +/- 0.024 mg/kg/wk vs 0.307 +/- 0. 03 mg/kg/wk for carriers of CYP2C9*2, CYP2C9*3, or CYP2A6*2 p olymorphism; P = .03). Conclusions. Polymorphisms that impair warfarin metabolism are common, occu rring in 34% of patients, and are associated with increased warfarin sensit ivity. The use of genotypic information to prescribe more accurate doses of warfarin may increase the safety and efficacy of this medication.