Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Sensitivity to Coumarin Derivatives [T88.7]

OMIM numbers: 122700, 601130 (CYP2C9), 608547 (VKORC1)

Dipl.-Biol. Birgit Busse

Scientific Background

High variability in individual dosage and the risk of an over- or underanticoagulation can complicate treatment with vitamin K antagonists (e.g. warfarin, phenprocoumon). Severe bleeding or resistance to treatment may be the consequence.

Sensitivity to vitamin K antagonists is partially determined by the CYP2C9 genotype. The alleles CYP2C9*2 and CYP2C9*3 are associated with a reduced metabolism of coumarin derivatives. Carriers of these alleles need lower doses of the medication to maintain a therapeutically effective level.  The C>T polymorphism rs9934438 in nucleotide position 1173 in the gene of the vitamin K epoxide reductase (VKORC1) is associated with sensitivity as well as resistence to vitamin K antagonists. Carriers of the C allele need a higher daily maintenance dose of vitamin K antagonists to reach a therapeutically sufficient anticoagulation than carriers of T alleles. Among all Caucasians, frequency of the T allele is approximately 40%. The two polymorphisms in the CYP2C9 and VKORC1 gene may explain up to 55% of the interindividual dosage variances in the treatment with vitamin K antagonists. Moreover, co-medication, secondary diseases, and demographic co-factors (BMI, age, diet etc.) have a major influence. In patients requiring especially high or low doses, analysis of the CYP2C9 and VKORC1 genes can have a positive impact on treatment.