CYP4F2 and VKORC1 Genotyping

CYP4F2 and VKORC1 variation greatly affect the half-life of warfarin (Coumadin®) and the time it takes to reach a stable dose. VKORC1 is the site of action of warfarin. The level of the enzyme is under genetic control according to the DNA sequence present in the control region of the gene. Inherited differences in VKORC1 increase or decrease the amount of warfarin needed to inhibit the formation of the clotting factors.[42] When the amount of warfarin exceeds what is needed, the risk of bleeding is increased.

CYP4F2 Poor and Intermediate Metabolizers have decreased CYP4F2 activity and may require a higher dose of warfarin to achieve therapeutic anticoagulation. The frequency of the CYP4F2 variant among European American is 30% and 8% among African Americans.[43]

Results may be used for initial warfarin dose titration along with CYP2C9, CYP4F2 and VKORC1. Consult label or www.warfarindosing.org for dosing advice and adjust warfarin dose based on INR and concurrent medications. Indications for testing include lack of therapeutic effect or difficulties with side effects of warfarin. Genetic variants tested are CYP4F2 c.1297G>A and VKORC1 c.-1639G>A. Analytical specificity and sensitivity for detection of these mutations are >99%.

Indication for CYP2C19 Testing

For individuals with a personal or family history of adverse drug reactions to warfarin.