The Contribution of VKORC1 and CYP2C9 Genetic Polymorphisms and Patients’ Demographic Characteristics with Warfarin Maintenance Doses: A Suggested Warfarin Dosing Algorithm

Document Type : Research article

Authors

1 Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.

2 Department of Pharmacology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran

3 Department of Cardiovascular Surgery, Seyyed-al-Shohada Heart Center, Urmia University of Medical Sciences, Urmia, Iran.

Abstract

The requirement of varying doses of warfarin for different individuals can be explained by environmental and genetic factors. We evaluated the frequency of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) variants together with patientdemographic characteristics and investigated their association with warfarin dose requirement with the objective to suggest a warfarin dosing algorithm. In this study, 185 patients with heart valve replacement from West Azerbaijan, Iran were genotyped for VKORC1 (-1639 G>A) and CYP2C9 (*2 and *3 alleles) by PCR-RFLP. Multiple linear regression was performed to create a new warfarin dosing algorithm. The frequency of variants in studied subjects was 12% for CYP2C9 *2, 25.8% for CYP2C9 *3, and 60% for -1639A. The patients who carried the A allele at position -1639 VKORC1 and the variants CYP2C9 *2 and *3 required a significantly lower daily mean warfarin dosage (P = 0.001). Statistical analysis also indicated a significant relationship between the daily maintenance dose of warfarin with age and blood pressure among the studied patients’ cohort (P < 0.001). This study showed that in the heart valve replacement patients considering VKORC1 and CYP2C9 polymorphisms beside demographic characteristics such as age will be helpful in pre-treatment dosing of warfarin which in turn reduces the complications associated with inappropriate warfarin dosing.

Graphical Abstract

The Contribution of  VKORC1 and CYP2C9 Genetic Polymorphisms and Patients’ Demographic Characteristics with Warfarin Maintenance Doses: A Suggested Warfarin Dosing Algorithm

Keywords


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