VKORC1 (-1639) Polymorphisms do not Affect Long-Term Stability of Anticoagulation with Warfarin

The extent of INR fall following vitamin K supplementation to patients on warfarin is related to VKORC1-1639G>A genotype, with those carrying the GG genotype demonstrating a significantly larger fall in INR compared to those carrying the GA, and AA genotype. We hypothesized that, due to the expected variability in dietary vitamin K intake over time, patients with the VKORC1(-1639)GG polymorphism could have poorer anticoagulation control than GA or AA carriers. 234 atrial fibrillation (AF) patients on warfarin therapy were studied. Anticoagulation control was assessed by the determination of percentage time in therapeutic range (% TTR) of INR, the frequency of INR monitoring and warfarin dose changes over a 12 months period. There were no significant differences between GG GA and AA variants in mean % TTR (66, 61, 68), mean number of INR monitoring events (12.4, 13.5, 13.0) and mean warfarin dose changes (3.9, 4.0, 3.3), respectively. The study results failed to confirm our hypothesis that patients with the VKORC1(-1639) GG variant have poorer anticoagulation control, indicating that the effect of any such influence at the pharmacological level is too small to influence clinically relevant outcomes in our population.