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VKORC1 (-1639) Polymorphisms do not affect long-term stability of anticoagulation Background Previously we demonstrated that the extent of INR fall following vitamin K supplementation to patients on warfarin and with unstable control varies between different patients and is related to VKORC1-1639G>A genotype, with those carrying the GG genotype demonstrating a significantly larger fall in INR, and requiring a significantly greater increase in warfarin dose compared to those carrying the GA, and AA genotype. Objectives We hypothesized that patients on warfarin therapy with the VKORC1(-1639)GG polymorphism could be most sensitive to day to day variability in dietary intake of vitamin K and, as a result, have less stable control of anticoagulation than those with GA or AA genotypes. Aim To examine the effect of VKORC1 polymorphism on long-term anticoagulation control in a cohort of patients on chronic warfarin therapy Patients/Methods 234 atrial fibrillation patients on chronic warfarin therapy with known VKORC1 polymorphism were studied. Anticoagulation control was assessed by the determination of %TTR and the frequency of INR monitoring and warfarin dose changes over a 12 months period. Results and Conclusions The prevalence of VKORC1 AA, GA, and GG variants was 18.4%, 56.4%, and 25.2% respectively. There were no significant differences between the three variants (GG GA AA) in mean %TTR (66, 61, 68), mean number of INR monitoring events (12.4, 13.5, 13.0) and mean dose changes (3.9, 4.0, 3.3), respectively. The study results failed to confirm our hypothesis that variations in daily dietary vitamin K intake might lead to poorer INR stability in patients with the VKORC1- G1639A variant, indicating that the effect of any such influence at the pharmacological level is too small to influence clinically relevant outcome.
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