Oral anticoagulants: Pharmacogenetics Relationship between genetic and non-genetic factors.
Oral 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.
D'Andrea
Giovanna
G
Genetica Medica, Dipartimento di Scienze Biomediche, Università di Foggia, Italy.
D'Ambrosio
Rosa
R
Margaglione
Maurizio
M
D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001779:Blood Coagulation Factors / Q000235:genetics; D003374:Coumarins / Q000378:metabolism / Q000494:pharmacology; D065729:Cytochrome P-450 CYP2C9; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D064417:Vitamin K Epoxide Reductases
D000925:Anticoagulants; D001779:Blood Coagulation Factors; D003374:Coumarins; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases