title: Pharmacogenetics of warfarin: development of a dosing algorithm for brazilian patients.
abstract: 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).
authors.affiliation: Divisão de Farmacologia, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: J A
authors.initials: JA
authors.lastname: Perini
authors.forename: C J
authors.initials: CJ
authors.lastname: Struchiner
authors.forename: E
authors.initials: E
authors.lastname: Silva-Assunção
authors.forename: I S C
authors.initials: IS
authors.lastname: Santana
authors.forename: F
authors.initials: F
authors.lastname: Rangel
authors.forename: E B
authors.initials: EB
authors.lastname: Ojopi
authors.forename: E
authors.initials: E
authors.lastname: Dias-Neto
authors.forename: G
authors.initials: G
authors.lastname: Suarez-Kurtz