PHARMACOGENETICS OF COUMARINS
(VKORC1 AND CYP2C9 GENE TESTS)
Background
Coumarins, such as warfarin and phenprocoumon, are vitamin K agonists that have been widely used as orally administered anticoagulants for therapy and prophylaxis of thromboembolic conditions. Due to its narrow effective therapeutic concentration ranges and broad variation in required individual dosage, clinical management of coumarin therapy may be demanding.
Vitamin K epoxide reductase (VKORC1), the main target of coumarins, carries a common G/A polymorphism which plays an important role in coumarin dose. Additionally, cytochrome CYP2C9 is essential for the metabolism of coumarins. Defective CYP2C9 gene variants (*2, *3) lead to reduced enzymatic degradation of coumarins, resulting in lower coumarin dosages and an increased tendency to severe overanticoagulation and retarded stabilization.
VKORC1 genotypes
| Genotype | Frequency | Commentary |
| VKORC1 -1639 GG | 38% | Lower coumarin sensitivity (higher dosage of coumarin may be required) |
| VKORC1 -1639 GA | 43% | Normal coumarin sensitivity |
| VKORC1 -1639 AA | 19% | Higher coumarin sensitivity (lower dosage of coumarins may be required) |
CYP2C9 genotypes
| Genotype | Frequency | Commentary |
| CYP2C9 *1*1 | 67% | wild-type genotype |
| CYP2C9 *1*2 or *1*3 (heterozygous deficiency) |
29% | Heterozygous CYP2C9 deficiency (Lower dosage of coumarins may be required, increased risk for over-anticoagulation) |
| CYP2C9 *2*2, *2*3, *3*3 (homozygous deficiency) |
4% | Homozygous CYP2C9 deficiency (Lower dosage of coumarins may be required, increased risk for over-anticoagulation) |
Indications for testing
Specimen Shipping
Literature:
