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

Authors

  • Behnam Askari Department of Cardiovascular Surgery, Seyyed-al-Shohada Heart Center, Urmia University of Medical Sciences, Urmia, Iran.
  • Esmat Khaleqsefat Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
  • Hamid Soraya Department of Pharmacology, Faculty of Pharmacy, 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.

Upgrade to premium to download articles

Sign up to access the full text

Already have an account?login

similar resources

Testing of VKORC1 and CYP2C9 alleles to guide warfarin dosing

Warfarin is an oral anticoagulant that is widely prescribed to prevent thromboembolic events in persons at increased risk. The optimal dose is difficult to establish because it can vary 10-fold among individuals due to clinical and demographic factors. Testing for variants of the vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) genes has been proposed for use in g...

full text

The effect of CYP2C9 and VKORC1 genetic polymorphisms on warfarin dose requirements in a pediatric population

OBJECTIVE The aim was to investigate the frequency of genetic polymorphisms of cytochrome P4502C9 (CYP2C9) and vitamin K epoxide reductase complex subunit1 (VKORC1) and determine the effect of these polymorphisms on warfarin dose requirements in pediatric patients. METHODS Fifty-eight pediatric patients with cardiac disease, thrombophilia, or other conditions, taking a stable warfarin dose, a...

full text

Warfarin Dosing in a Patient with CYP2C9∗3∗3 and VKORC1-1639 AA Genotypes

Genetic factors most correlated with warfarin dose requirements are variations in the genes encoding the enzymes cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKOR). Patients receiving warfarin who possess one or more genetic variations in CYP2C9 and VKORC1 are at increased risk of adverse drug events and require significant dose reductions to achieve a therapeutic international...

full text

VKORC1 and CYP2C9 Genotype Variations in Relation to Warfarin Dosing in Korean Stroke Patients

BACKGROUND AND PURPOSE Variant alleles of CYP2C9 and VKORC1 account for differences in anticoagulation response. We sought to establish a warfarin dosing formula for individualized target International Normalization Ratio of Prothrombin Times (INRs) using data from single nucleotide polymorphisms (SNPs) in VKORC1 and CYP2C9 in Korean patients. METHODS Ischemic stroke patients displaying stabl...

full text

Effect of Cyp2c9 and Vkorc1 Genetic Polymorphisms on Warfarin Dose Requirement in South Indian Population

Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genetic polymorphisms were strongly associated with warfarin dose requirement in Caucasians, African Americans and other populations. Our aim was to evaluate the effect of CYP2C9 and VKORC1 genetic polymorphisms on warfarin dose requirement in south Indian population. A total of 150 patients on warfarin with...

full text

My Resources

Save resource for easier access later

Save to my library Already added to my library

{@ msg_add @}


Journal title

volume 19  issue 3

pages  77- 85

publication date 2020-09-01

By following a journal you will be notified via email when a new issue of this journal is published.

Hosted on Doprax cloud platform doprax.com

copyright © 2015-2023