Warfarin (CYP2C9 and VKORC1) Genotyping


Related Gene(s): CYP2C9, VKORC1

The human cytochrome P450 superfamily is responsible for metabolizing exogenous and endogenous substrates. The cytochrome P450-2C9 (CYP2C9) enzyme contributes to the metabolism of a large number of clinically relevant drug classes and drugs, including anticoagulants (eg, warfarin), sulfonylureas, NSAIDs, phenytoin, and angiotensin II blockers (eg, losartan). The CYP2C9 gene is located within a cluster of cytochrome P450 genes (centromere-CYP2C18-CYP2C19-CYP2C9-CYP2C8-telomere) on chromosome 10q23.33. The CYP2C9 gene has nine exons and is highly polymorphic, with over 60 variant star (*) alleles currently defined by the Human Cytochrome P450 Allele Nomenclature Committee.

The VKORC1 gene encodes the vitamin K epoxide reductase protein, which is the target enzyme of warfarin. VKORC1 catalyzes the conversion of vitamin K-epoxide to vitamin K, which is the rate-limiting step in vitamin K recycling. A common promoter variant of VKORC1 (c.-1639G>A, rs9923231) is significantly associated with warfarin sensitivity and reduced dose requirements.

The strong association between variant CYP2C9 alleles and VKORC1 c.-1639G>A with therapeutic warfarin dose requirements has prompted their inclusion into publicly available warfarin dosing algorithms: Warfarindosing.org and the International Warfarin Pharmacogenetics Consortium (IWPC).

This targeted genotyping test interrogates the following variants:CYP2C9 – decreased function (*2, *3, *4, *5) and no function (*6); VKORC1 – warfarin sensitivity (c.-1639G>A (rs9923231)).


Specimen Requirements

Postnatal

  • Anticoagulated blood: Two 5-10 mL tubes with EDTA (lavender top) are preferred. ACD tubes (yellow top) are also accepted
  • Additionally, we can accept saliva specimens

Ordering Information

Shipping

  • Ship at room temperature

Turnaround Time

  • 24-48 hours


Resources

Consent and requisition forms available soon. For additional assistance, please contact us.