Pharmacogenetic testing for personalization of warfarin dosing
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Abstract
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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