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

• Published in: Iranian journal of pharmaceutical research : IJPR Vol. 19; no. 3; pp. 77 - 85
• Main Authors: Khaleqsefat, Esmat, Khalaj-Kondori, Mohammad, Jabarpour Bonyadi, Mortaza, Soraya, Hamid, Askari, Behnam
• Format: Journal Article
• Language: English
• Published: Iran Shaheed Beheshti University of Medical Sciences 01.01.2020
• Subjects: Original; VKORC1; CYP2C9; Warfarin; Genetic Polymorphism; Demographic Characteristics
• ISSN: 1735-0328; 1726-6890
• DOI: 10.22037/ijpr.2020.1101116

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 ( ) and cytochrome P450 2C9 ( ) 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 (-1639 G>A) and (*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 *2, 25.8% for  *3, and 60% for -1639A. The patients who carried the A allele at position -1639 and the variants *2 and *3 required a significantly lower daily mean warfarin dosage ( = 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 < 0.001). This study showed that in the heart valve replacement patients considering and 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.