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2009 | 50 | 4 | 399-403
Article title

A vitamin K epoxide reductase-oxidase complex gene polymorphism (?1639G>A) and interindividual variability in the dose-effect of vitamin K antagonists

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EN
Abstracts
EN
A daily dose of vitamin K antagonists (VKAs) may vary and its range depends on various interrelated factors. Low responsiveness to VKA (defined as a failure to achieve a target international normalized ratio [INR]) is associated with polymorphisms of the vitamin K epoxide reductase-oxidase complex gene (VKORC1). A highly prevalent promoter single-nucleotide polymorphism (VKORC1-1639 G>A, rs17878363) impairs VKORC1 expression and determines the interindividual variability of the target INR. We studied 57 patients receiving oral anticoagulation, including 50 subjects treated with acenocoumarol (mean dose: 5.7+-2.3 mg/day) and 7 treated with warfarin (mean dose: 9.6+-4.2 mg/day). The indications for the use of oral anticoagulant therapy were as follows: deep-vein thrombosis (N = 23); pulmonary embolism (N = 20); arterial thrombosis (N = 5); stroke (N = 4); atrial fibrillation with transient ischemic attacks (N = 2), and history of multiple thromboembolic events (N = 3). Identification of the VKORC1 genomic variation was performed using DNA sequencing methods. The prevalence of the mutated allele (VKORC1 -1639A) was 41%. The VKORC1 -1639G allele carriers required a higher daily dose of acenocoumarol (5.9+-1.9 mg) than the noncarriers (4.1+-3.3 mg; P < 0.001). All of 5 low responders (who failed to achieve a target INR using standard dose requirements of VKAs) were homozygous for the 1639G allele. Low responders did not differ from good responders with respect to age, gender, and body mass index. Our findings suggest the potential benefits from pharmacogenetic testing, and provide evidence that the VKORC1 -1639 G>A gene polymorphism may explain at least in part the low responsiveness to acenocoumarol.
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Year
Volume
50
Issue
4
Pages
399-403
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author
author
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References
Document Type
ARTICLE
Publication order reference
E. Stepien, John Paul II Hospital, Pradnicka 80, 31?202 Krakow, Poland
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YADDA identifier
bwmeta1.element.element-from-psjc-07ab6af1-6eb3-3043-82bf-c0a0dce970db
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