Influence of VKORC1-1639G＞A and CYP2C9*3 polymorphisms, age and body weight on warfarin stable dose in Han Chinese patients with pulmonary thromboembolism

Abstract

Objective To develope individualized warfarin dose,we investigated the impact of cytochrome P450 2C9(CYP2C9) gene and vitamin K epoxide reductase complex subunit 1 (VKORC1)gene polymorphisms and non-genetic factors on warfarin dose in Han Chinese patients with pulmonary thromboembolism (PTE).Methods We selected 185 patients from Beijing Anzhen Hospital with PTE who have been prescribed warfarin with a 2.0-3.0 range of prothrombin time normalized as an international normalized ratio for at least 3 months.VKORC1-1639G＞A and CYP2C9*3 were genotyped by the way of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).We developed a warfarin stable dose predictive algorithm by multivariate stepwise regression analysis.Results There were great inter-individual differences in warfarin stable dose in 185 patients,ranging from a minimum dose of 1.5 mg/d to a maximal dose of 7.5 mg/d.Spearman rank correlation analysis revealed that warfarin stable dose was significantly correlated with VKORC1-1639 genotype,CYP2C9*3 genotype and age.There was no significant difference between warfarin stable dose and sex,height,weight,BSA and mean INR values.Stepwise multiple linear regression resulted in the following final algorithm of warfarin stable dose:D=5.802-1.780× (VKORC1-1639AG)-3.395 × (VKORC1-1639AA)-0.027×Age+1.36×(CYP2C9*1/*1)+0.018 ×Weight.The regression equation could account for 51.7％ of overall inter-individual variation in warfarin stable dose.Conclusions VKORC1-1639G＞A and CYP2C9*3 gene polymorphisms,age and body weight were found to affect the inter-individual warfarin dosage variability in Han Chinese patients with PTE. Key words: Polymorphism; VKORC1; CYP2C9; Warfarin; Pulmonary thromboembolism