Identify individuals with inherited variants that affect metabolism of (CYP2C8, CYP2C9) or sensitivity to (CYP4F2, VKORC1) warfarin.
Polymerase Chain Reaction/Fluorescence Monitoring
Whole Blood: Lavender (EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).
Saliva: Collection Device by DNA Genotek (OCD-100, ARUP Supply #49295) available online through eSupply using ARUP Connect™ or by contacting ARUP Client Services at (800) 522-2787.
Transport 3 mL whole blood. (Min: 1 mL) OR Transport the Saliva Collection Device.
Whole Blood: Refrigerated.
Saliva: Room temperature.
Plasma or serum. Specimens collected in sodium heparin or lithium heparin.
Whole Blood: Ambient: 72 hours; Refrigerated: 1 week; Frozen: 1 month
Saliva: Ambient: 2 weeks; Refrigerated: Unacceptable; Frozen: Unacceptable
Background Information for Warfarin Sensitivity (CYP2C8, CYP2C9, CYP4F2, VKORC1) Genotyping:
Characteristics: Warfarin sensitivity can lead to a life-threatening overdose event such as excessive bleeding. Genetic variation is recognized to explain a large proportion of variability in warfarin dose requirements. This test may predict individual warfarin sensitivity and non-standard dose requirements. The cytochrome P450 (CYP) isozymes 2C8 and 2C9 are involved in the metabolism of many drugs. Variants in the genes that code for CYP2C8 and CYP2C9 may influence pharmacokinetics of substrates such as warfarin, and may predict or explain non-standard dose requirements, therapeutic failure or adverse reactions. Variants in the VKORC1 and CYP4F2 genes may predict sensitivity to warfarin. Genetic information and non-genetic factors can be used in combination with warfarin dose calculators, such as through www.WarfarinDosing.org.
Inheritance: Autosomal codominant.
Cause: CYP2C8, CYP2C9 and CYP4F2 gene variants affect enzyme expression or activity. The VKORC1*2 allele is associated with reduced expression of the warfarin target, vitamin K epoxide reductase (VKOR), and a reduced dose requirement. The CYP4F2 variant tested is associated with an increased dose requirement.
Variants Tested: See the "Additional Technical Information" document.
Clinical Sensitivity: Genetic factors and known non-genetic factors account for approximately 50 percent of the variability in warfarin dose.
Methodology: Polymerase chain reaction (PCR) and fluorescence monitoring.
Analytical Sensitivity and Specificity: Greater than 99 percent.
Limitations: Only the targeted CYP2C8, CYP2C9, CYP4F2 and VKORC1 variants will be detected by this panel, and assumptions about phase and content are made to assign alleles. Publically available sources such as the www.pharmvar.org or www.pharmgkb.org provide guidance on phenotype predictions and allele frequencies. Diagnostic errors can occur due to rare sequence variations. Risk of therapeutic failure or adverse reactions with CYP2C8 or CYP2C9 substrates may be affected by genetic and non-genetic factors that are not detected by this test. This result does not replace the need for therapeutic drug or clinical monitoring.
Please note the information contained in this report does not contain medication recommendations, and should not be interpreted as recommending any specific medications. Any dosage adjustments or other changes to medications should be evaluated in consultation with a medical provider.
Compliance Statement C: For human genetic inheritable conditions and mutations. This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
Whole blood is the preferred specimen. Saliva samples that yield inadequate DNA quality and/or quantity will be reported as inconclusive if test performance does not meet laboratory-determined criteria for reporting.
|Component Test Code*||Component Chart Name||LOINC|
|3001542||WARF PAN Specimen||31208-2|
|3001545||WARF PAN Interpretation|