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- DME Genotyping
Warfarin, the coumadin derivative, is the most widely prescribed anticoagulant for thromboembolic disorders.
The metabolism of drugs is also influenced by ethnicity, diet, and other medications. All factors should be considered prior to initiating new therapy.
Real-time polymerase chain reaction (PCR)
VKORC1 (vitamin K epoxide reductase complex subunit 1) and cytochrome P450 CYP2C9 account for as much as 50% of the interindividual variability of the warfarin response. These genetic markers may serve as clinically relevant predictors of warfarin dosing.
The presence of the promoter mutation -1639G>A in the VKORC1 gene reduces the gene's expression and leads to combined deficiency of vitamin K-dependent coagulation factors type 2 (VKCFD2). The risk of bleeding complication during oral anticoagulation is high. Low-dosage warfarin treatment should be considered. Analysis of the VKORC1 gene targets the 1173C>T mutation, which is in linkage disequilibrium with -1639G>A and thus carries identical diagnostic utility.
The presence of the *2 and/or *3 alleles in the CYP2C9 gene can result in poor metabolizer (PM) phenotypes. The PM phenotype is associated with lack of enzyme activity, and the drug may be metabolized slowly or not at all. This results in increased concentrations of the drug with a reduced or absent therapeutic response and the potential for serious side effects. Warfarin metabolism is reduced by 30% to 50% by the *2 allele and 90% by the *3 allele. This affect may be more pronounced in Asians as compared to Caucasians. Individuals with at least one copy of *2 or *3 have an increased risk of bleeding compared to individuals without *2 or *3. A lower maintenance dose may be required. Coadministration of inhibitors of CYP2C9, such as phenylbutazone, sulfinpyrazone, amiodarone, miconazole, isoniazid, ticlopidine, tamoxifen, or fluconazole, will increase the anticoagulation effect. The azole antifungal agent fluconazole (Diflucan) is a potent inhibitor of CYP2C9. Fluconazole, at conventional doses, abolishes CYP2C9 activity. Rifampin, barbiturates, carbamazepine, and St John's Wort will increase warfarin metabolism and increase the chance of reduced efficacy, and the warfarin dose may need to be increased.
Whole blood or LabCorp buccal swab kit (buccal swab collection kit contains instructions for use of a buccal swab)
7 mL whole blood or LabCorp buccal swab kit
3 mL whole blood or two buccal swabs
Maintain specimen at room temperature or refrigerate at 4°C.
Causes for Rejection
Frozen specimen; hemolysis; quantity not sufficient for analysis; improper container; one buccal swab; wet buccal swab
|Order Code||Order Code Name||Order Loinc||Result Code||Result Code Name||UofM||Result LOINC|
|511460||Warfarin (p450 2C9 and VKORC1)||511461||2C9 Genotype||46724-1|
|511460||Warfarin (p450 2C9 and VKORC1)||511462||VKORC1 Genotype||50722-8|
|511460||Warfarin (p450 2C9 and VKORC1)||511466||Interpretation:||62365-2|
|511460||Warfarin (p450 2C9 and VKORC1)||511467||Comment:||77202-0|
|511460||Warfarin (p450 2C9 and VKORC1)||511471||Methodology:||49549-9|
|511460||Warfarin (p450 2C9 and VKORC1)||511469||Director Review:||72486-4|