Warfarin Sensitivity Genotyping

Warfarin (Coumadin) is the most widely prescribed oral anticoagulant drug for the prevention and treatment of thrombotic disorders in North America1. Warfarin is a potent inhibitor of VKORC1 (vitamin K epoxide reductase complex, subunit 1), which is required for converting to Vitamin K to its reduced form (VitKH2). Anticoagulation occurs when Warfarin inhibits VKOR, decreasing the amount of VitKH2 available to activate vitamin K-dependent coagulation factors II, VII, IX, and X2,3.

While Warfarin is a well-accepted therapy for many conditions, it has some serious side effects including excessive bleeding that can be life-threatening. Because of genetic variations, different people may response to Warfarin differently and thus be under dosed or overdosed. Patients with a variation, -1639G>A, in the promoter region of VKORC1 gene are more sensitive to warfarin and need lower doses than those without the variation. The CYP2C9 gene encodes one of the main enzymes involved in metabolizing warfarin into inactive hydroxylated metabolites. Several CYP2C9 alleles such as CYP2C9*2 and CYP2C9*3 are associated with reduced enzyme activity to convert warfarin into inactive form. Patients carrying at least one copy of such a variant allele will need a lower daily warfarin dose than those having normal CYP2C9 activity.

The MutectorTM Warfarin Genotyping Kit is a single tube test with simple procedures and has reliable results in 3-4 hours.

ASSAY INFORMATION
Target SNPs             CYP2C9 *2, *3, VKORC1 -1639G>A
Assay Platform        Capillary sequencer ABI 3100, 3700, 3130, 3500
Assay Format           One tube test
Sample Request      20-160 ng DNA from whole blood or buccal swab            
Assay Workflow

ORDER INFORMATION

Cat. No. Product NameGene Alleles Interrogated SizeDocuments
GP03Warfarin Genotyping kitCYP2C9 *2, *3, VKORC1 -1639G>A*32 rxnManual

For research use only. Not for use in diagnostic procedures.   * VKORC1 primer is not included in the kit

DATA
Results of Warfarin Genotyping Test 
Single tube simultaneously detects CYP2C9*2CYP2C9*3 and VKORC1* -1639G>A:

 Example of genotyping results - DNA sample extracted from buccal swab using Trimgen's Buccal Quick:

* The primer for VKORC1 is not included in the kit. 

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References

  1. Holbrook AM et al. (2005). Systematic overview of warfarin and its drug and food interactions. Arch. Intern. Med. 165:1095
  2. Ansell J at al. (2008). Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 133(6 Suppl):160S
  3. Moyer TP at al. (2009). Warfarin sensitivity genotyping: a review of the literature and summary of patient experience. Mayo Clin Proc. 84:1079