VKORC1 -1639G/A and 1173 C/T Genetic Polymorphisms Influence Individual Differences in Warfarin Maintenance Dose.

Objective: In this study, we investigated two VKORC1 gene polymorphisms, -1639G/A and 1173C/T, for effects on warfarin maintenance dosage in valvular heart disease (VHD) patients after cardiac valve replacement (CVR).

Methods: A total of 219 VHD patients receiving warfarin therapy after CVR surgery were recruited to this study between June 2010 and December 2013. Basic clinical data, prothrombin time, warfarin maintenance dose, and blood samples were collected from all patients. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses were used to analyze the VKORC1 -1639G/A and 1173C/T polymorphisms. SPSS version 19.0 software was used for statistical analysis of the data.

Results: Patients with either the AG+or GG genotype (n=32) of the VKORC1 -1639G/A polymorphism required a significantly higher warfarin dose compared to patients with the AA genotype (n=187) (4.36±1.03 mg/day vs. 2.95±0.94 mg/day; p<0.001). Similarly, patients carrying the CT genotype (n=28) of the VKORC1 1173C/T polymorphism also required a significantly higher warfarin dose compared to those with the TT genotype (n=191) (4.19±0.99 mg/day vs. 3.00±0.94 mg/day; p<0.001). Linear regression analysis showed that gender, age, weight, and VKORC1 -1639G/A and 1173C/T polymorphisms were correlated with individual differences in warfarin maintenance dose (all p<0.05).

Conclusion: We present evidence that the two VKORC1 polymorphisms, -1639G/A and 1173C/T, are key genetic factors influencing individual differences in warfarin maintenance dose in VHD patients who underwent CVR. Gender, age, and weight also independently correlated with warfarin maintenance dose.