Significant inter-individual variability on the effect of vitamin K to reverse overanticoagulation has been identified. Genetic polymorphisms of the vitamin K epoxide reductase complex subunit 1 (VKORC1) gene might explain in part this variability. The objective of this study was to evaluate the influence of VKORC1 ?
1639G>
A and
3730G>
A polymorphisms on the effect of oral vitamin K supplementation in overanticoagulated patients. We performed an interventional trial of oral vitamin K supplementation in over-anticoagulated outpatients (international normalized ratio [INR] ≥ 4). Subjects received vitamin K (2.5–5.0 mg) according to baseline INR and were genotyped by real time polymerase chain reaction (PCR). INR values were determined at 3, 6, 24 and 72 h after supplementation. We evaluated 33 outpatients, 61 % were males, with a mean age of 62 ± 12 years old. There was a significant decrease in INR values over time for both polymorphisms after oral vitamin K. At 3 h after supplementation, patients carrying the
G allele for the ?
1639G>
A polymorphism had a greater decrease in INR values compared to
AA patients (
p < 0.05 for difference among groups;
p < 0.001 for time variation;
p = 0.001 for time × group interaction), with differences of ?1.01 for
GG versus
AA (
p = 0.003) and ?0.84 for
GA versus
AA (
p = 0.024). Mean INR value at 24 h was 1.9 ± 0.6 and at 72 h was 2.1 ± 0.7, with no differences among genotypes. No significant interaction was identified between the
3730G>
A polymorphism and vitamin K supplementation. Our study indicated that the VKORC1 ?
1639G>
A polymorphism plays a role in the response to acute vitamin K supplementation in over-anticoagulated patients, with faster decrease of INR value in patients carrying the
G allele.
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