Oral anticoagulants: Pharmacogenetics: Relationship between genetic and non-genetic factors

SummaryOral anticoagulants, the main drugs used for the prevention and treatment of thromboembolic diseases, exhibit a greater than 10-fold inter-individual variability in the dose requirement to achieve a therapeutic response. The relationship between the dose prescribed and the individual response is regulated by genetic and environmental factors. In particularly, molecular analysis of two genes, encoding for the enzyme responsible for the warfarin (S)-isoform catabolism (CYP2C9) and for the target enzyme vitamin K epoxide reductase complex 1 (VKORC1), strongly suggested that their genetic variations greatly affect the individual response to oral anticoagulants. Genotype based modelling explained a large amount of dose-variations. As a perspective, it appears meaningful to increase the number of candidate genes involved in the metabolism of oral anticoagulants to set up a powerful tool, easy for a rapid use into all laboratories and clinical settings, to improve the oral anticoagulants therapy management.