RESUMEN
Background: Polymorphisms in the CYP2C9, VKORC1, MDR1 and APOE genes may impact warfarin dose. Aim: To investigate the influence of sociodemographic, clinical factors and polymorphisms *1, *2 and *3 for CYP2C9, -1639G>A for VKORC1, 3435C>T for MDR1, and ϵ2, ϵ3 and ϵ4 for APOE genes on the mean weekly warfarin maintenance dose in adults. Methods: This cross-sectional study recruited a calculated sample of 315 patients in three anticoagulation clinics in Brazil. A model containing the variables significantly associated with warfarin dose was estimated. Results: The mean age of patients was 64.1 ± 13.1 years, with 173 (54.9%) women. Age, use of amiodarone, genotype VKORC1 GA, genotype VKORC1 AA, genotypes CYP2C9*1/*2 or *1/*3 and genotypes CYP2C9*2/*2 or *2/*3 or *3/*3 were associated with a reduced warfarin dose. Conclusion: This study pointed out factors that could impact the management of oral anticoagulation.
RESUMEN
Warfarin exhibits a wide variation in dose requirements. We sought to evaluate the association of polymorphisms CYP2C9*2 (rs1799853), CYP2C9*3 (rs1075910), and VKORC1-G1639A (rs9923231) and nongenetic factors with maintenance doses of warfarin <17.5 mg/week and to create an algorithm to predict drug sensitivity. This is a retrospective cohort study including 312 patients assisted at an anticoagulation clinic in Brazil. The mean age of participants was 60.4 ± 13.5 years and 59.9% were female. The logistic regression model included: age [odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01-1.06], genotype VKORC1 AA (OR 31.61, 95% CI 11.20-100.15) and genotype CYP2C9 2/2, 2/3 or 3/3 (OR 16.48, 95% CI 3.37-81.79). The creation of our algorithm involved warfarin-experienced patients on stable doses, identifying factors associated with drug sensitivity. The validation of this algorithm allows its use in future populations to determine the initial dose distinguishing patients with dose requirements <17.5 mg and reducing time to achieve stable doses.