The Algorithm with Multiple Genotypes on Optimal Warfarin Doses in Korean Patients

Background and Objectives Genetic factors that affect warfarin dose are not routinely evaluated in the Korean population. In this study, we investigated the influence of genetic polymorphisms (GPs) on optimal warfarin dose (OWD) and derived an OWD prediction algorithm based on Korean patients with various diseases requiring anticoagulation therapy. Methods One hundred eight patients taking warfarin were included. We evaluated clinical characteristics, OWD, international normalized ratio (INR), VKORC1, CYP2C9, and CYP4F2 polymorphisms, as well as medication information. OWD was defined as the maintenance dose that kept a patient’s INR within the target range based on at least two consecutive laboratory measurements separated by more one 1 week. Results The 108 patients (mean age: 61.5± 12.4 yr, 48% male) had a mean OWD of 3.12± 1.30 (1-9) mg/day. VKORC1 wild-type patients (AA) had a lower OWD than VKORC1 variant patients (GA). Significantly more OWD patients had the CYP2C9 wild-type genotype than CYP2C9 mutant genotypes. Among the three genotypes of CYP4F2, two carriers had a significantly higher OWD than patients who had the wildtype genotype. We derived an OWD algorithm that included VKORC1, CYP2C9, CYP4F2, body mass index (BMI), age, amiodarone use, and diuretic use. Conclusion Our algorithm was capable of explaining 41.8% of the total variation in warfarin dose in our patient cohort. Multiple GPs affect the OWD in Korean patients.