The c.-1639G > A polymorphism of the VKORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients.

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Montes R, Ruiz de Gaona E, Martinez-Gonzalez MA, Alberca I, Hermida J

The c.-1639G > A polymorphism of the VKORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients.

Br J Haematol. 2006 Apr;133(2):183-7.

PubMed ID

16611310 [ View in PubMed

]

Abstract

Much of the variability in the sensitivity to warfarin in anticoagulated patients is associated with the c.-1639G > A polymorphism of the vitamin K-epoxide reductase (VKORC1) gene. However, its association with the acenocoumarol dose in patients under anticoagulant therapy has not been studied. The c.-1639G > A genotype of VKORC1 was determined in 113 patients on stable anticoagulation requiring low (n = 42), medium (n = 42) or high (n = 21) acenocoumarol doses. To evaluate the association between acenocoumarol requirements and the c.-1639G > A variant, multivariate logistic regression models were fitted, adjusting for age, gender, and the c.430C > T and c.1075A > C variants of cytochrome P450 2C9 (CYP2C9). A total of 90.5% of the patients in the low acenocoumarol dose group carried the A allele of VKORC1:c.-1639G > A. The A allele independently increased the odds of requiring a low acenocoumarol dose [odds ratio (OR) 9.4; 95% confidence interval (CI) 1.9-46.4; P = 0.006], especially when the homozygous form was present (OR 44.2; 95% CI 5.5-354.6; P < 0.001). The A allele was less frequent in the high dose group showing an inverse association with the requirement for high doses (OR 0.04; 95% CI 0.01-0.22; P < 0.001). The A allele of the c.-1639G > A polymorphism of VKORC1 is therefore associated with a low-dose requirement for acenocoumarol in patients receiving anticoagulant therapy.

DrugBank Data that Cites this Article

Drugs

Acenocoumarol

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Acenocoumarol	Vitamin K epoxide reductase complex subunit 1	Protein	Humans	Yes	Inhibitor	Details