L'ubica Krajčíová1, Robert Petrovič, L'udmila Déžiová, Ján Chandoga, Peter Turčáni. 1. 1st Department of Neurology, University Hospital, Bratislava, Slovakia; Institute of Medical Biology, Genetics and Clinical Genetics, Comenius University Faculty of Medicine and University Hospital, Bratislava, Slovakia.
Abstract
OBJECTIVE: Warfarin represents the most commonly prescribed oral anticoagulants, which functions as an antagonist of vitamin K, an essential factor of blood coagulation cascade. Warfarin has a narrow therapeutic index. An insufficient dose can cause failure of antithrombotic effect, and an overdose increases a risk of bleeding. It is known that variability in two genes (CYP2C9 and VKORC1) has a significant effect on individual response to warfarin dose. These polymorphisms influence more than one-third of known warfarin dose effect. Pharmacogenetics of warfarin is less affected by polymorphisms in the other genes such as CYP4F2, CYP2C19, and GGCX. MATERIAL AND METHODS: The frequency of selected single nucleotide polymorphisms including CYP2C9*2 (430C > T), CYP2C9*3 (1075A > C), VKORC1*2 (-1639G > A/1173C > T), VKORC1*3 (3730G > A), GGCX (12970C > G, 8016G > A), CYP2C19*2 (681G > A), and CYP4F2*3 (1297G > A) was tested in a control group consisting of 112 randomly selected individuals by allele-specific real-time PCR, restriction fragment length polymorphism, and bidirectional PCR allele-specific amplification. RESULTS AND DISCUSSION: The current results were statistically evaluated and compared with other populations. The presented results in Slovak population which is in Hardy-Weinberg equilibrium were compared with the prevalence in different countries. The incidence of selected polymorphisms in Slovak population correlates with Caucasians.
OBJECTIVE:Warfarin represents the most commonly prescribed oral anticoagulants, which functions as an antagonist of vitamin K, an essential factor of blood coagulation cascade. Warfarin has a narrow therapeutic index. An insufficient dose can cause failure of antithrombotic effect, and an overdose increases a risk of bleeding. It is known that variability in two genes (CYP2C9 and VKORC1) has a significant effect on individual response to warfarin dose. These polymorphisms influence more than one-third of known warfarin dose effect. Pharmacogenetics of warfarin is less affected by polymorphisms in the other genes such as CYP4F2, CYP2C19, and GGCX. MATERIAL AND METHODS: The frequency of selected single nucleotide polymorphisms including CYP2C9*2 (430C > T), CYP2C9*3 (1075A > C), VKORC1*2 (-1639G > A/1173C > T), VKORC1*3 (3730G > A), GGCX (12970C > G, 8016G > A), CYP2C19*2 (681G > A), and CYP4F2*3 (1297G > A) was tested in a control group consisting of 112 randomly selected individuals by allele-specific real-time PCR, restriction fragment length polymorphism, and bidirectional PCR allele-specific amplification. RESULTS AND DISCUSSION: The current results were statistically evaluated and compared with other populations. The presented results in Slovak population which is in Hardy-Weinberg equilibrium were compared with the prevalence in different countries. The incidence of selected polymorphisms in Slovak population correlates with Caucasians.