Warfarin PGXL Genotyping: Cytochrome P450 2C9 and VKORC1 (-1639 G>A) Combination Genotyping
Test Code
Cytochrome P450 2C9 (CYP2C9) and Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1), CYP2C9+VKORC1
CPT Codes
83891 x1; 83892 x2; 83900 x1; 83901 x3; 83914 x6; 83909 x1; 83912 x1; 83912-25 x1
Specimen
Whole blood or buccal swabs
Volume
5 mL of whole blood or four buccal swabs
Minimum Volume
3 mL of whole blood or four buccal swabs
Container
Lavender-stopper (EDTA) tube or paper envelope for dried buccal swabs
Storage Instructions
Maintain at room temperature or refrigerate
Cause for Rejection
Hemolyzed specimen; quantity not sufficient
Use
Warfarin is the most commonly prescribed anticoagulant for the treatment and prevention of thromboembolic events. The anticoagulant effect of warfarin is due to the inhibition of the vitamin K epoxide reductase enzyme, leading to a reduction of the vitamin K pool and an inability to activate the vitamin K-dependent clotting factors. The active component of warfarin is metabolized by cytochrome P450 2C9 (CYP2C9). Polymorphisms in the CYP2C9 gene are associated with decreased warfarin clearance and an increased risk of bleeding. An additional polymorphism in the vitamin K epoxide reductase complex subunit 1 (VKORC1) gene is also associated with warfarin sensitivity and decreased maintenance dose requirements of the medication.
By testing for the inherited differences in CYP2C9 and VKORC1 and taking into consideration patient physical characteristics, PGXL can estimate individual warfarin daily maintenance dosages, and subsequently identify those patients who will require low dose. Thus, the potential for bleeding events and other adverse drug reactions can be reduced.
For more information, download our Warfarin guide (pdf)
Limitations
Known or unknown variants in either gene that are not detected in this assay may affect warfarin dose requirement. The maintenance dose of warfarin is also influenced by concomitant medications, diet and various disease states. All factors should be considered prior to initiating new therapy.
Methodology
Multiplex polymerase chain reaction and allele-specific primer extension (Tag-It (TM)).
Turnaround Time
Five business days after receipt of specimen. STAT turnaround time of 3 business days is available for an additional charge.
References
Reynolds KK et al. Individualizing warfarin therapy. Pers Med 2007;4(1):11-31.
Zhu Y et al. Estimation of warfarin maintenance dose requirements based on VKORC1 and CYP2C9 gene polymorphisms and rationale for application in clinical practice. Clin Chem 2007
Sconce EA et al. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood 2005 Oct 1;106(7):2329-33.
Bodin L et al. A vitamin K epoxide reductase complex subunit-1 (VKORC1) mutation in a patient with vitamin K antagonist resistance. J Thromb Haemost 2005 Jul;3(7):1533-5.
Rieder MJ et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N Engl J Med 2005 Jun 2;352(22):2285-93
Linder MW et al. Warfarin dose adjustments based on CYP2C9 genetic polymorphisms. J Thromb Thrombolysis 2002 Dec;14(3):227-32