RESUMEN

There is controversy regarding the association between the CYP4F2 rs2108622 (V33M) polymorphism and warfarin dose requirement in white patients, and there are no data for nonwhite populations. We observed no association in self-identified white, black, or "intermediate" Brazilian patients (n = 370). The addition of the rs2108622 genotype as a variable has only a marginal effect on the predictive power of a warfarin dosing algorithm derived from this patient cohort. We conclude that prospective CYP4F2 genotyping is not justified in Brazilians who are potential candidates for warfarin therapy.

Asunto(s)

Anticoagulantes/administración & dosificación , Sistema Enzimático del Citocromo P-450/genética , Grupos Raciales/genética , Warfarina/administración & dosificación , Algoritmos , Población Negra/genética , Brasil , Estudios de Cohortes , Familia 4 del Citocromo P450 , Relación Dosis-Respuesta a Droga , Humanos , Polimorfismo Genético , Estudios Retrospectivos , Población Blanca/genética

RESUMEN

A dosing algorithm including genetic (VKORC1 and CYP2C9 genotypes) and nongenetic factors (age, weight, therapeutic indication, and cotreatment with amiodarone or simvastatin) explained 51% of the variance in stable weekly warfarin doses in 390 patients attending an anticoagulant clinic in a Brazilian public hospital. The VKORC1 3673G>A genotype was the most important predictor of warfarin dose, with a partial R(2) value of 23.9%. Replacing the VKORC1 3673G>A genotype with VKORC1 diplotype did not increase the algorithm's predictive power. We suggest that three other single-nucleotide polymorphisms (SNPs) (5808T>G, 6853G>C, and 9041G>A) that are in strong linkage disequilibrium (LD) with 3673G>A would be equally good predictors of the warfarin dose requirement. The algorithm's predictive power was similar across the self-identified "race/color" subsets. "Race/color" was not associated with stable warfarin dose in the multiple regression model, although the required warfarin dose was significantly lower (P = 0.006) in white (29 +/- 13 mg/week, n = 196) than in black patients (35 +/- 15 mg/week, n = 76).

Asunto(s)

Algoritmos , Hidrocarburo de Aril Hidroxilasas/genética , Oxigenasas de Función Mixta/genética , Farmacogenética , Polimorfismo Genético , Warfarina/farmacocinética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Atención Ambulatoria , Amiodarona/administración & dosificación , Amiodarona/farmacocinética , Análisis de Varianza , Hidrocarburo de Aril Hidroxilasas/efectos de los fármacos , Brasil , Estudios de Cohortes , Citocromo P-450 CYP2C9 , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Etnicidad/genética , Femenino , Genotipo , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Oxigenasas de Función Mixta/efectos de los fármacos , Análisis Multivariante , Estudios Retrospectivos , Medición de Riesgo , Sensibilidad y Especificidad , Simvastatina/administración & dosificación , Simvastatina/farmacocinética , Resultado del Tratamiento , Vitamina K Epóxido Reductasas , Warfarina/administración & dosificación , Adulto Joven