CYP2C19, CYP2C9, VKORC1
Features
■ Comprehensive:
Genotype the genes responsible for Clopidogrel and Warfarin metabolism at one time.
Workflow
Sample types
Loci detected
Application
Clopidogrel is commonly prescribed for ACSs and/or following PCI. Clopidogrel is a thienopyridine prodrug that requires CYP2C19 enzyme to form an active metabolite and drug response varies due to CYP2C19 gene polymorphism.
The wild-type CYP2C19*1 allele is associated with functional CYP2C19-mediated metabolism. The most common CYP2C19 loss-of-function alleles are *2 and *3, which can reduce active clopidogrel metabolites and higher on-treatment platelet aggregation as compared with *1 homozygotes. By contrast, the CYP2C19*17 allele has higher activity, which results in enhanced platelet inhibition and clopidogrel response, and perhaps, an increased risk of bleeding complications.
Warfarin is a widely used anticoagulant with a narrow therapeutic index and large interpatient variability in the dose required to achieve target anticoagulation. CYP2C19 is the primary metabolizing enzyme of S-warfarin. Compared to patients homozygous for CYP2C19*1, individuals who inherit one or two copies of CYP2C19*2 or *3 are at greater risk of bleeding during warfarin therapy, require lower doses to achieve similar levels of anticoagulation, and require more time to achieve a stable INR. VKORC1 encodes the vitamin K epoxide reductase protein, the target enzyme of warfarin. A common variant upstream of VKORC1 (c.-1639G>A, rs9923231) is significantly associated with warfarin sensitivity.