Warfarin dose requirements with different genotypes of CYP2C9 and VKORC1 for patients with atrial fibrillation and valve replacement

Aims: To investigate whether genetic variants of CYP2C9 and VKORC1 have different effects on the dose of warfarin in 180 Han Chinese patients who were recruited from the Fu Wai Hospital. All were on maintenance treatment with stable daily warfarin doses for a period of at least 3 months. Methods: DNA was isolated and genotyped using a Warfarin dosage Prediction Kit for single nucleotide polymorphisms (SNPs) of CYP2C9 and VKORC1. Results: The VKORC1 and CYP2C9*3 polymorphisms are significantly associated with warfarin maintenance dosages. Patients with AG&GG genotype in VKORC1 needed higher doses than those with AA genotypes (4.55 +/- 1.27 mg/ day vs. 2.90 +/- 0.97 mg/day, p < 0.001). Patients with *1/*3 genotype in CYP2C9 need doses lower than those with *1/*1 genotypes (1.73 +/- 0.95 mg/day vs. 3.23 +/- 1.13 mg/day, p < 0.001). There were no significant differences between the warfarin maintenance dosages in patients with atrial fibrillation (3.09 +/- 1.16 mg/day), patients with heart valve replacement (2.95 +/- 1.21 mg/day) and those with both atrial fibrillation and heart valve replacement (3.36 +/- 1.13 mg/day) (p > 0.05). The mean warfarin daily dose requirements in the genotypes of VKORC1 and CYP2C9 were not dependent on the medical indication(s) present. Conclusions: Genetic variants of CYP2C9, VKORC1, and age are significant determinants of the maintenance dose of warfarin. The medical indications atrial fibrillation, valve replacement, or a combination of both are not determinants of the warfarin dose requirements.