Cor Vasa 2011, 53(10):522-526 | DOI: 10.33678/cor.2011.131

Prevalence of polymorphisms of CYP2C9 and VKORC1 in the Czech Republic and reflection on the views of anticoagulation therapy with warfarin

Jan Kvasnička^1,*, Jaroslava Hájková¹, Petra Bobčíková¹, Tomáš Kvasnička¹, Daniela Dušková², Šárka Poletínová², Veronika Kieferová², Ladislav Pecen³

¹ Trombotické centrum a Centrální hematologické laboratoře, Ústav klinické biochemie a laboratorní diagnostiky, Všeobecná fakultní nemocnice a 1. lékařská fakulta Univerzity Karlovy, Praha

² Fakultní transfuzní oddělení, Všeobecná fakultní nemocnice a 1. lékařská fakulta Univerzity Karlovy, Praha

³ Ústav informatiky Akademie věd ČR, Praha, Česká republika

Introduction: Polymorphisms in the genes encoding the cytochrome P 450 2C9 enzyme and the vitamin K epoxide reductase, subunit 1 (VKORC1) are known to contribute to the sensitivity to warfarin.
Aim of the study: We wanted to determine the prevalence of CYP2C9 (allele *1, *2 and *3) and VKORC1 (-1639 G and A alleles), and their combinations in Czech population to get an idea of how many percent of individuals can theoretically involve increased sensitivity to warfarin.

Methods: Genotyping was performed in 1300 healthy subjects (774 men and 526 women) using a robotic DNA isolation and subsequent PCR amplification according to the manufacturer's instructions with melting curve analysis (Light Cycler 480 System, Roche).

Results: The combinations of VKORC1 -1639 A/A genotypes with CYP2C9 *1/*3, *2/*2, *2/*3 or *3/*3, and a rare combination of VKORC1 -1639 G/A with CYP2C9 *3/*3, which underlie very high sensitivity to warfarin, were determined in 1.6% of people. The combinations of VKORC1 -1639 A/A with CYP2C9 *1/*2, VKORC1 -1639 G/A with CYP2C9 *2/*3, and VKORC1 -1639 G/G with CYP2C9 *3/*3, which underlie high sensitivity to warfarin, were determined in 3.3% of people. The combinations of VKORC1 -1639 A/A with CYP2C9 *1/*1, and VKORC1 -1639 G/A with the CYP2C9 *1/*2, *1/*3, *2/*2 or VKORC1 -1639 G/G with CYP2/C *2/*3, which underlie medium-high sensitivity to warfarin, were determined in 26.2% of people.

Conclusion: About 30% of the Czech healthy subjects have genetically determined higher sensitivity to warfarin. New antithrombotics use is discussed as an alternative to warfarin.

Keywords: Warfarin; Prevalence of CYP2C9 mutations; Prevalence of VKORC1 mutation; Czech Republic; New antithrombotics

Published: October 1, 2011  Show citation