Impact of CYP4F2 rs2108622 on the stable warfarin dose in an admixed patient cohort.

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.

Pharmacogenetics of warfarin: development of a dosing algorithm for brazilian patients.

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).