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VKORC1 G1639A

VKORC1 G1639A Screening test for: Metabolism of Warfarin Therapy with warfarin - or acenocoumarol - is the most widely used anticoagulant treatment in medical and surgical practice of many chronic diseases. However, due to the complex dose-response relationship and the narrow therapeutic window of warfarin, bleeding complications occur frequently. Although has long been known that the enzyme involved in the metabolism of warfarin is the CYP2C9, belonging to the cytochrome P450 system, and that its gene polymorphisms CYP2C9 * 2 and CYP2C9 * 3 are associated with an altered metabolism of warfarin, only recently, thanks to the characterization of the genes of the molecular target of coumarins VKORC1 (gene coding for vitamin K epoxide reductase complex 1), and the association of its polymorphism-1639G> A with the polymorphisms of CYP2C9, was possible to have an innovative pharmacogenetic tool applicable in clinical practice of anticoagulation therapy.

In fact, it has been observed that subjects carriers of both alleles mutated in the VKORC1 gene (AA mutated genotype ) require maintenance doses of coumarins minors and exhibit a lower expression of mRNA for VKORC1 than carriers of a single mutant allele (genotype G / A) or both wild-type alleles (genotype GG). At the level of the promoter of the VKORC1 gene, the polymorphism-1639G> A modulates the expression of the gene and the relative amount of mRNA. VKORC1-1639G is the normal allele, and VKORC1-1639A allele is the variant with reduced expression.

There are then three possible genotypes at the level of the VKORC1 nucleotide position -1639: G / G, G / A, A / A. In general, to obtain the adequate therapeutic level anticoagulant, subjects with genotypes -1639 A / A and A / G require a lower dose of warfarin compared to individuals with genotype G / G. The genotypes for the polymorphisms of CYP2C9 and VKORC1 gene of a particular subject matter contribute to the determination of the therapeutic dose of warfarin. 

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