Frequency of selected single nucleotide polymorphisms influencing the warfarin pharmacogenetics in Slovak population.

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.