title: Influence of VKORC1 gene polymorphisms on the effect of oral vitamin K supplementation in over-anticoagulated patients.
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.
authors.affiliation: Post-Graduate Program in Health Science, Cardiology and Cardiovascular Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Priccila
authors.initials: P
authors.lastname: Zuchinali
authors.forename: Gabriela C
authors.initials: GC
authors.lastname: Souza
authors.forename: Graziella
authors.initials: G
authors.lastname: Aliti
authors.forename: Mariana R
authors.initials: MR
authors.lastname: Botton
authors.forename: Lívia
authors.initials: L
authors.lastname: Goldraich
authors.forename: Katia G
authors.initials: KG
authors.lastname: Santos
authors.forename: Mara H
authors.initials: MH
authors.lastname: Hutz
authors.forename: Eliane
authors.initials: E
authors.lastname: Bandinelli
authors.forename: Luis E
authors.initials: LE
authors.lastname: Rohde
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000483:Alleles; D000925:Anticoagulants / Q000008:administration & dosage*; D000933:Antifibrinolytic Agents / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014812:Vitamin K / Q000008:administration & dosage*; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*
chemical_list: D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D014812:Vitamin K; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases