Warfarin Pharmacogenetics Test (CYP2C9 & VKORC1) - 3 Variants (8000101269) | |||||||||||||||||||||||||||||||||||
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Test Mnemonic: | |||||||||||||||||||||||||||||||||||
Specimen Requirements: | Whole Blood |
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Collection: | 3ml |
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Container: | lavender top (EDTA), pink (K2EDTA), blue (Na Citrate) or yellow (Acid Citrate Dextrose) collection tube |
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Minimum Volume: | 1ml |
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Storage/Transport: | Ambient |
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Stability: | 30 days |
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Causes for Rejection: | Incorrect tube, Inadequate volume |
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Reference Range: | Negative |
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Turnaround Time: | 1-7 days, please contact Molecular Diagnostics (409-772-4197) for quicker result. |
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Methodology: | Genmark eSensor |
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Performed: | |||||||||||||||||||||||||||||||||||
Lab: | Molecular Diagnostics Laboratory |
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Synonyms: | Warfarin, Coumadin, Warfarin Sensitivity, CYP2C9, 2C9, Cytochrome P450 2C9, P450 2C9 Genotyping, Vitamin K Epoxide Reductase Complex, VKORC1 |
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CPT 4 Code: | 81227, 81355 |
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Note: |
Characteristics: Warfarin (Coumadin) is metabolized primarily in the liver by cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and exerts its anticoagulant effect by inhibiting vitamin K epoxide reductase complex, subunit 1 (VKORC1). Three single nucleotide polymorphisms, two in the CYP2C9 and one in the VKORC1 genes, have been found to play key roles in determining the effect of warfarin therapy on coagulation. This test may predict individual warfarin sensitivity and non-standard dose requirements.
Inheritance: Autosomal co-dominant. Variants Tested: CYP2C9 (variants are numbered according to NM_000771): *2 (rs1799853, c.430C>T) and *3 (rs1057910, c.1075A>C). CYP2C9 *2 and *3 variants result in decreased enzyme activity that will reduce metabolism and prolong the half-life of warfarin. Negative, *1 (reference allele at all positions). VKORC1 (variant is numbered according to NM_024006): VKORC1-1639 G>A polymorphism (rs9923231, c.-1639G>A). The VKORC1-1639A allele is associated with reduced expression of VKORC1 and a reduced dose requirement. Negative, the common VKORC1-1639G allele. Allele Frequencies: CYP2C9: 11% and 7% of Caucasians carry the *2 and *3 variants, respectively. Both variants are rare (< 2%) in African Americans or Asians.
VKORC1-1639A: Caucasians 37 percent, Asians 91 percent, African Americans 14 percent.
Clinical Sensitivity: Approximately 90 percent of CYP2C9 and VKORC1 variants causing warfarin sensitivity in Caucasians are detected when both tests are performed. Less characterized in other populations. Methodology: Multiplex polymerase chain reaction and eSensor XT-8 System (GenMark Diagnostics). The U.S. Food and Drug Administration (FDA) has approved or cleared this test.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Only the targeted CYP2C9 and VKORC1 variants will be detected by this test. Diagnostic errors can occur due to rare sequence variations. Risk of therapeutic failure or adverse reactions with warfarin 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. This test does not identify patients at risk for warfarin resistance. Table 1. Expected maintenance warfarin daily doses (mg/day) based on CYP2C9 and VKORC1 genotypes (reproduced from updated warfarin FDA product label)
References: OMIM: http://omim.org/entry/601130, and http://omim.org/entry/608547 PharmGKB: https://www.pharmgkb.org/, updated Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines. Warfarin and CYP2C9/VKORC1: https://www.pharmgkb.org/molecule/PA451906 CYP2C9: https://www.pharmgkb.org/gene/PA126 VKORC1: https://www.pharmgkb.org/gene/PA133787052 WarfarinDosing.org: http://www.warfarindosing.org/Source/Home.aspx Counseling and informed consent are recommended for genetic testing. |
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When ordering tests for which Medicare or Medicaid reimbursement will be sought, physicians should only order tests that are medically necessary for the diagnosis or treatment of the patient. Components of the organ or disease panels may be ordered individually. The diagnostic information must substantiate all tests ordered and must be in the form of an ICD-10 code or its verbal equivalent. |