O.O. Melnyk Pharmacogenetic testing for personalization of warfarin dosing

The sensitivity to warfarin is influenced by genetic factors, which are determined by polymorphisms of the genes CYP2C9 and VKORC1. In case of the wild type – CYP2C9*1, the rate of warfarin metabolism is standard. In the presence of variants of CYP2C9*2 and CYP2C9*3, the activity of the enzyme is reduced, therefore these alleles are «slow metabolizers» and patients need a lower, in comparison with the standard, dose of warfarin. VKORC1 (Vitamin K Epoxide Reductase Complex, subunit 1) is a main enzyme that activates vitamin K. The polymorphisms of VKORC1 can significantly alter pharmacodynamics of warfarin and the requirements for a maintenance dose. Patients with 1639A (rs992323) and 1173T (rs9934438) alleles require lower dose of warfarin (mean dose 24–26 mg/week) compared to 35 mg/week for wild type. While patients with 9041A (rs7294) require a higher dose of warfarin (an average dose 40 mg/week). With timely performance of pharmacogenetic testing it may be possible to identify patients who need an individual dose of warfarin and accordingly to reduce the percentage of complications.

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