Which are the genes affecting steady-state dose of warfarin?

We know that therapeutic dose of warfarin varies from individual to individual. That is why we need regular monitoring of prothrombin time with international normalized ratio (PT-INR). Though there are several reasons for variations in prothrombin time, genetic factors are also important. Single Nucleotide Polymorphisms (SNP) of three genes can affect warfarin steady state does due to their effect on warfarin metabolism. CYP2C9, VKORC1 and CYP4F2 are these important genes. VKORC1 and CYP2C9 variants account for almost half of the variability in warfarin steady-state dose. Bleeding risk has been associated with CYP2C9*3 and variant CYP4F2 [1].

CYP2C9 stands for Cytochrome P450 family 2 subfamily C member 9. It is important in the metabolism of drugs including warfarin. VKORC1 stands for Vitamin K epoxide reductase complex subunit 1. It is responsible for reducing vitamin K 2,3-epoxide to its active form. CYP4F2 is a gene that encodes a protein called Cytochrome P450 4F2, involved in the metabolism of drugs like warfarin.

References

1. Braunwald’s Textbook of Heart Disease, 12th Edition, Page 95.