Diagnosis: Pharmacogenomics of warfarin
• Warfarin is metabolized by oxidation in the liver by CYP2C9. The mechanism of action of warfarin is the inhibition of the vitamin K epoxide reductase complex, subunit 1.
• VKORC1 and CYP2C9 are two genes with single nucleotide polymorphisms that predict variable response to warfarin metabolism.
• CYP2C9 is a P450 enzyme involved in warfarin metabolism. The variant alleles CYP2C9*2 and CYP2C9*3 metabolize warfarin more slowly and may require a lower initial dose.
• VKORC1 encodes the vitamin K epoxide reductase gene. Variable alleles are associated with variable metabolism of warfarin. Individuals with the group A haplotype produce less VKORC1, and lower warfarin doses are needed in these patients.
• The CYP2C9 and VKORC1 alleles are found in different frequencies based on ethnic background. For example, the VKORC1 group A haplotype associated with lower warfarin requirements is present in 89% of Asians, but the group B haplotype is seen more in whites and African Americans.
