Effect of CYP2C9 and VKORC1 genetic polymorphisms on mean daily maintenance dose of acenocoumarol in South Indian patients

Aim: To determine the effect of CYP2C9 and VKORC1 genetic polymorphisms on mean daily maintenance dose of acenocoumarol in South Indian patients with heart valve replacement. Materials and methods: The study was conducted in 170 patients on therapy with acenocoumarol following heart valve replacement surgery. Single nucleotide polymorphisms (SNP) namely CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), and VKORC1 (rs9923231) were identified by quantitative Real-Time Polymerase Chain Reaction (RT-PCR) method. Results: Patients with at least one variant allele of CYP2C9 (*1*2 or *1*3) required 44% and 28.2% lower daily maintenance dose of acenocoumarol (2.0 mg and 2.5 mg, respectively) than the normal CYP2C9*1*1 genotype group (3.4 mg) (p<0.05). Patients with VKORC1 GG genotype required higher dose (3.3 mg) as compared to those with genotype VKORC1 GA (2.3 mg) and VKORC1 AA (1.0 mg) (p<0.001). Patients with both CYP2C9*1*2/*1*3 and VKORC1 GA genotype required 38% lower dose (2.46 mg) than patients with CYP2C9*1*1 and VKORC1 GG genotype (3.52 mg) (p<0.0001). The clinical (age, body mass index) and genetic variables (VKORC1-1639 G>A, CYP2C9*2, CYP2C9*3) contribute together to predict 30.4% of the required maintenance dose of acenocoumarol. Conclusion: The genetic polymorphisms of CYP2C9 and VKORC1 results in decreased requirement of daily maintenance dose of acenocoumarol. The polymorphism VKORC1 (-1639 G>A) was found to be the major predictor of acenocoumarol dose requirement in South Indian population. (C) 2013 Elsevier Ltd. All rights reserved.