untitled protocol v1

Background: Warfarin is an oral anticoagulant associated with adverse reaction drugs due to wide inter- and intra-individual dosage variability. Warfarin dosage has been related to non-genetic and genetic factors. CYP2C9 and VKORC1 gene polymorphisms influence warfarin metabolism and dosage. Due to the central role of populations’ ethnical and genetic origin on warfarin dosage variability, novel algorithms for Latin American subgroups are necessary to establish safe anticoagulation therapy. Patients and Methods: We assessed CYP2C9*2 (c.430C>T), CYP2C9*3 (c.1075A>C), CYP4F2 (c.1297G>A) and VKORC1 (-1639G>A) polymorphisms in 152 patients who received warfarin. We evaluated the impact on the variability of patients’ warfarin dose requirements. Multiple linear regression analysis, using genetic and non-genetic variables, was used for creating an algorithm for optimal warfarin maintenance dose. Results: Median weekly prescribed warfarin dosage was significantly lower in patients having the VKORC1 -1639 AA genotype and poor CYP2C9*2/*2,*2/*3 metabolizers than their WT counterparts. We found a 2.3-fold increase in mean dose for normal sensitivity patients (wild type VKORC1/CYP2C9 genotypes) compared to the other groups (moderate and high sensitivity); 31.5% of the patients in our study group had warfarin sensitivity-related genotypes. The estimated regression equation accounted for 44.4% of overall variability regarding warfarin maintenance dose. The algorithm was validated, giving 45.9% correlation (R2=0.459). Conclusions: Our results describe and validate the first algorithm for predicting warfarin dose in a Colombian mestizo population and have contributed towards understanding pharmacogenetics in a Latin America population subgroup.