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Influence of VKORC1 gene polymorphisms on the effect of oral vitamin K supplementation in over-anticoagulated patients

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Abstract

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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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Post-Graduate Program in Health Science, Cardiology and Cardiovascular Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil

    Priccila Zuchinali, Lívia Goldraich, Katia G. Santos & Luis E. Rohde

  2. Department of Internal Medicine, Medical School, Federal University of Rio Grande do Sul, Porto Alegre, Brazil

    Gabriela C. Souza & Luis E. Rohde

  3. Nursing School, Federal University of Rio Grande do Sul, Porto Alegre, Brazil

    Graziella Aliti

  4. Post-Graduate Program in Genetics and Molecular Biology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil

    Mariana R. Botton

  5. Department of Genetics, Institute of Biosciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil

    Mara H. Hutz & Eliane Bandinelli

  6. Division of Cardiology, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, Room 2061, Porto Alegre, RS, 90035-003, Brazil

    Luis E. Rohde

  7. Cardiovascular Division, Federal University of Rio Grande do Sul, Porto Alegre, Brazil

    Lívia Goldraich

Authors
  1. Priccila Zuchinali
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  2. Gabriela C. Souza
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  3. Graziella Aliti
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  4. Mariana R. Botton
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  6. Katia G. Santos
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  7. Mara H. Hutz
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  8. Eliane Bandinelli
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  9. Luis E. Rohde
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Correspondence to Luis E. Rohde.

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Zuchinali, P., Souza, G.C., Aliti, G. et al. Influence of VKORC1 gene polymorphisms on the effect of oral vitamin K supplementation in over-anticoagulated patients. J Thromb Thrombolysis 37, 338–344 (2014). https://doi.org/10.1007/s11239-013-0947-3

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  • DOI: https://doi.org/10.1007/s11239-013-0947-3

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