Cytochrome P450 CYP2C9 and VKORC1 Genotyping

CYP2C9 acts on 15% of drugs in current clinical use. About 35% of Caucasians have a slow acting form of this enzyme. CYP2C9 is an important drug-metabolizing enzyme that catalyzes the biotransformation of many other clinically useful drugs including angiotensin II blockers, non-steroidal anti-inflammatory drugs, the alkylating anticancer prodrugs, sulfonylureas and many others.

Of special interest are those drugs with narrow therapeutic index, such as S-warfarin, tolbutamide and phenytoin, where impairment in CYP2C9 metabolic activity might cause difficulties in dose adjustment as well as toxicity. Indications for testing include lack of therapeutic effect or difficulties with side effects to any of the drugs metabolized by CYP2C9.

CYP2C9 and VKORC1 variation greatly affect the half-life of warfarin (Coumadin) and time to 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. When the amount of warfarin exceeds what is needed, the risk of bleeding is increased. Indications for testing include lack of therapeutic effect or difficulties with side effects to warfarin.

This test identifies the eight most common variants of CYP2C9 and a VKORC1 polymorphism (-1639G>A) which influences warfarin maintenance dose. Analytical specificity and sensitivity for detection of these mutations are >99%.

Indication for Testing
For individuals with a personal or family history of adverse drug reactions to warfarin and/or other medications metabolized by CYP2C9. Confirm presence of genotypes that affect the metabolism of any drugs that are metabolized by CYP2C9. Confirm presence of CYP2C9 and VKORC1 (-1639G>A) genotypes that affect metabolism of warfarin (Coumadin).

Specimen Types
Please call Client Services at 800-523-6487 to obtain specimen kits.

• Buccal Swabs: 4 sterile buccal swabs
• Blood: 5-10 cc whole blood lavender-top EDTA or Yellow-top ACD-A tubes
• Turnaround Time: 5 days, 4 day STAT

CPT Codes
(provided for guidance only)

CYP2C9 Mutation DNA Analysis:  81227