Pharmacogenomic impact of the determination of VKORC1 and CYP2C9 genes over the efficacy, safety and costs of the anticoagulant treatment, TROMBOGEN

Objectives:
to investigate the pharmacogenomic status of the patients, from both geno- andphenotypic point of view;
to reveal the polymorphism of the CYP2C9 and VKORC1 genes, and alsoof the genes involved in the thrombophilia phenomenon (Factor V Leiden, FII G20210A, PAI-1 4G/5G, MTHFR C677T and A1298C) and the possible relationship between the presence of these polymorphisms and the response to acenocumarol treatment;

OBJECTIVES	to investigate the pharmacogenomic status of the patients, from both geno- andphenotypic point of view; to reveal the polymorphism of the CYP2C9 and VKORC1 genes, and alsoof the genes involved in the thrombophilia phenomenon (Factor V Leiden, FII G20210A, PAI-1 4G/5G, MTHFR C677T and A1298C) and the possible relationship between the presence of these polymorphisms and the response to acenocumarol treatment; to adapt the acenocumarol treatment to the individual genetic constellation of the individuals, through a multidisciplinary approach, which will increase the medical act’s and the patient’s life quality, achieving a positive costs to benefits ratio and elaborating a personalized treatment.
DESCRIPTION	Thromboembolic disease unifies two clinical entities – deep vein thrombosis (DVT) and pulmonaryembolism (PE) – and represents an important chapter of the cardiovascular diseases, regarding bothincidence and problems issued by prophylaxis and therapy. Atrial fibrillation is the most common form of persistent arrhythmias, which demands long-term anticoagulant treatment in order to decrease the riskof thromboembolic accidents. Acenocumarol, a coumarinic derivative, is used for the prophylaxis and treatment of thromboembolic disease and the complications of atrial fibrillation. Monitoring the treatment with acenocumarol is difficult in the context of great interindividual variability of the therapeutic response; leading to an elevated risk for side effects, especially hemorrhage. Acenocumarol is a drug with low therapeutic index, for which the dose-effect relation is hard to predict.The usual dosing algorithm of acenocumarol doesn’t count with individual genetic particularities, whichcould influence the treatment. The study of pharmacogenomic aspects could anticipate the efficiency ofthe anticoagulant treatment and, in the same time, the risk of side effects appearance, permitting the individualization of the therapy. TROMBO-GEN finds its justification in a series of studies of great actuality worldwide, each of theseinvestigating the correlation between the polymorphism of genes involved in the process of coagulation (VKORC1, CYP2C9) and the sensitivity to acenocumarol treatment. Until to the present day, there were no similar researches conducted in our country. The study is oriented on real treatment problems,both from the point of view of efficiency and safety of acenocumarol treatment, for which it will offersolutions, and of the economic factor.
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