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

• Autorzy: Stepien E , Branicka A , Ciesla-Dul M , Undas A
• Języki publikacji: EN

Abstrakty

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 responded (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 VKORCl -1639 G>A gene polymorphism may explain at least in part the low responsiveness to acenocoumarol.

Słowa kluczowe

EN

vitamin K; reductase-oxidase complex; gene polymorphism; interindividual variability; dose effect; antagonist; coumarin resistance; man; pharmacogenetics; polymorphism; thromboembolism

• Wydawca: -
• Czasopismo: Journal of Applied Genetics
• Rocznik: 2009
• Tom: 50
• Numer: 4
• Opis fizyczny: p.399-403,fig.,ref.

Twórcy

autor

Stepien E

• John Paul II Hospital, Pradnicka 80, 31-202 Krakow, Poland
• Institute of Cardiology, Jagiellonian University School of Medicine, Krakow, Poland

autor

Branicka A

• John Paul II Hospital, Pradnicka 80, 31-202 Krakow, Poland

autor

Ciesla-Dul M

• John Paul II Hospital, Pradnicka 80, 31-202 Krakow, Poland

autor

Undas A

• Institute of Cardiology, Jagiellonian University School of Medicine, Krakow, Poland

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