VKORC1

DuplicαRealTime VKORC1 1639G>A Genotyping Kit is an in vitro diagnostic test for the detection, by Real-Time PCR of the allelic variant g.1639G>A in the human gene coding for the sub-unit 1 of the vitamin K epoxide reductase enzyme complex.

Overview

Warfarin, a derivative of coumarin, is the most widely prescribed anticoagulant for the prevention and treatment of arterial and venous thromboembolic disease, including deep vein thrombosis (DVT), pulmonary embolism (PE), ischemic stroke, myocardial infarction (MI), and atrial fibrillation. However, optimizing the warfarin dose in individual patients is complicated by two factors. The first factor is the drug’s narrow therapeutic range, which leads to an increased risk of thromboembolism at lower doses and an increased risk of bleeding at higher doses. The second factor is the wide interindividual variability in warfarin response, influenced by multiple factors. Genetic variants are recognized to explain a large proportion of these factors. In particular, pharmacogenomic studies have identified a single nucleotide polymorphism (SNP) in the Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1) known as VKORC1 (1639G>A) that is an important determinant of the initial Warfarin dosage, along with two SNPs found in the cytochrome P450 enzyme gene CYP2C9 known as CYP2C9*2 (C430T) and CYP2C9*3 (A1075C). The VKORC1 gene encodes the vitamin K epoxide reductase protein which is the target of warfarin. Vitamin K helps activate several blood coagulation proteins and the VKORC1 enzyme then recycles the oxidized vitamin K back to its active form. Warfarin prevents this vitamin K recycling, hence depleting active vitamin K. The 1639G>A variant reduces the level of the VKORC1 enzyme by approximately 44%. This means that a lower dose of warfarin is required to achieve the same anticoagulant affect and it can be very easy to accidentally overdose with warfarin. The VKORC1 (1639G>A) test should be performed in combination with the CYP2C9 SNPs tests for application to warfarin dose estimates, such as through www.WarfarinDosing.org

Targets:

g.1639G>A polymorphism in the gene VKORC1
Internal Control (IC)

Diagnostic samples:

Peripheral whole blood samples collected in EDTA

DNA Extraction:

Compatible with the most common DNA Extraction and Purification Systems

Real-Time PCR instruments:

Compatible with the most common Real-Time PCR Systems