Laboratories  |  Physicians

CYP2C9/VKORC1 Genotyping Kit - Warfarin Sensitivity

Available Products

Product Name/Description
No. of Tests
Product Code
CYP2C9/VKORC1 Genotyping Reagents for Gel-Electrophoresis - RUO
50
WF-G50
CYP2C9/VKORC1 Genotyping Reagents for Gel-Electrophoresis - RUO
100
WF-G100

Entrogen’s warfarin sensitivity test is a polymerase chain reaction (PCR) -based assay that amplifies regions of the CYP2C9 and VKORC1 genes using allele specific oligonucleotide primers. This highly specific reaction produces bands of distinct sizes based on the genotype of the sample DNA. Genomic DNA can be easily extracted from whole blood or buccal swabs using readily available DNA isolation kits (ie. QIAamp DNA Blood Mini Kit). 

Detection of the PCR product is done using horizontal or capillary gel electrophoresis. The sizes of the amplicons are compared to those of known control samples for easy and accurate identification of the genotype.

Entrogen’s warfarin sensitivity test requires the following equipment:

  • Thermal cycler
  • Microcentrifuge
  • Horizontal gel electrophoresis or capillary electrophoresis apparatus
  • Gel documentation system (for horizontal gel electrophoresis only)

Warfarin (Coumadin®) is the most widely prescribed oral anticoagulant in North America and Europe with estimated 2 million patients receiving it in the U.S.A. every year. Warfarin therapy-associated hemorrhage is one of the leading causes of drug-related adverse events, including death, and is the second most common drug after insulin implicated in emergency room visits in the U.S. according to FDA data. The risk of severe bleeding is the highest when the drug introduced to a patient for the first time. American Enterprise Institute Brookings Report states that incorporating routine genetic testing into warfarin dosing will result in an estimated 85,000 fewer serious bleeds and 17,700 fewer strokes, resulting in savings of $1.1 billion (November 2006).

FDA Label. Warfarin has a notoriously narrow therapeutic index and a non-linear dose response creating a wide dosing range (50X) to achieve expected therapeutic outcome (target INR 2-3). A number of factors such as age, diet and weight have an affect. On August 17, 2007 FDA issued a warning to be included on the drug’s label to reflect that the genotypes of two genes play a major role in determining the proper dose of the medication. These include a gene encoding the drug metabolizing enzyme, CYP2C9 and the drug’s molecular target VKORC1.

Functional Interaction between warfarin, CYP2C9 and VKORC1. The active component of warfarin is metabolized by cytochrome P450 2C9 (CYP2C9). Up to 35% of the population inherits a form of the CYP2C9 gene variant that results in a CYP2C9 enzyme deficiency. A deficiency in CYP2C9 causes slow metabolism and higher than expected concentrations of the active drug in the body.1 Increased warfarin concentration in the body increases the risk of bleeding. Warfarin inhibits the formation of active clotting factors by inhibition of vitamin K epoxide reductase complex subunit 1 (VKORC1).2 Inherited variants of VKORC1 increase or decrease the amount of Warfarin needed to inhibit the formation of the clotting factors.3

Allele frequency in Caucasians, Africans and Asians:

Ethnic Group
CYP2C9*2
CYP2C9*3
VKORC1
(1639 G>A)
Caucasian 12.5% 7.0% 37%
African 3.4% 1.5% 14%
Asian 0% 1.8% 89%
Gage BF, Lesko LJ. J Thromb Thrombolysis. 2008 Feb;25(1):45-51

Reporting. The Warfarin Genetic Sensitivity test detects and reports on a total of three genetic variants: CYP2C9*2, CYP2C9*3 of cytochrome p450 and (-1639 G>A) in the promoter region of VKORC1 gene. CYP2C9*2 variant reduces Warfarin metabolism by 30% to 50% and CYP2C9*3 variant by 90%.4 Variant status (homozygous or heterozygous) as well as a functional phenotype result (normal or slow metabolism and normal or high sensitivity) are reported on.

Interpretation. The genotypes of CYP2C9 and VKORC1 along with the age, weight, gender, INR range and other characteristics can be used in a dosing algorithm available at www.warfarindosing.org.

Intended Use

EntroGen’s CYP2C9/VKORC1 Genotyping Kit is provided for research use only (RUO). Not for use in diagnostic procedures.

References

  1. Redman AR, Pharmacotherapy, 2001; 21:235–242.
  2. Li et al., Nature, 2004; 427:541–544
  3. Rieder et al., N Engl J Med, 2005; 352:2285–2293
  4. Gage et al., J Thromb Thrombolysis, 2008; 25(1):45-51

Product Overview

» Detects the 2 variants in CYP2C9 and 1 variant in VKORC1.
» Can be performed under 2 hours
» Simple setup and interpretation

Click here to request more information about this product.


© Copyright EntroGen, Inc 2008-2024.
All Rights Reserved.