Association of Warfarin Therapy with APOE and VKORC1 Genes Polymorphism in Iranian Population

Related Experiment Video

Updated: Feb 17, 2026

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene
07:00

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene

Published on: April 1, 2019

10.4K

Sajad Rafiee1, Masoumeh Rajabibazl1,2, Reza Meshkani3

  • 1Department of Clinical Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Iranian Journal of Pharmaceutical Research : IJPR
|December 5, 2017
PubMed

Insights

Genetic variations in VKORC1 influence warfarin dosing in Iranian patients. Patients with specific VKORC1 genotypes require lower warfarin doses, aiding personalized treatment strategies.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Genetics

Background:

  • Warfarin, a vitamin K antagonist, has variable dosing requirements influenced by genetic and non-genetic factors in cardiovascular disease patients.
  • Understanding these factors is crucial for optimizing warfarin therapy and minimizing adverse events.

Purpose of the Study:

  • To investigate the influence of VKORC1 and APOE gene polymorphisms on warfarin dose requirements in a cohort of Iranian patients.
  • To explore potential genetic markers for personalized warfarin dosing algorithms in this population.

Main Methods:

  • Genomic DNA was extracted from blood samples of 86 warfarin-treated patients.
  • VKORC1 (rs9923231) and APOE (rs429358, rs7412) polymorphisms were genotyped using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).

Main Results:

  • Patients with GA or AA genotypes of the VKORC1 polymorphism showed a trend towards requiring lower warfarin doses (p = 0.018).
  • The APOE E3/E3 genotype was more frequent (over 60%) in patients receiving low warfarin doses.
  • Body Mass Index (BMI) and weight correlated positively with warfarin dose, though not significantly (p > 0.05).

Conclusions:

  • VKORC1 polymorphisms significantly impact warfarin dose requirements in Iranian patients.
  • These findings can contribute to developing more precise warfarin dosing algorithms tailored for the Iranian population.
  • Further research is warranted to validate these genetic associations and integrate them into clinical practice.

Keywords:
APOE polymorphismsCardio vascular diseaseIranian populationVKORC1Warfarin therapy

More Related Videos

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

34.9K
Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer06:21

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Published on: May 10, 2024

1.3K

Related Concept Videos

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
10
Pharmacogenetics of Drug Metabolism: Overview01:27

Pharmacogenetics of Drug Metabolism: Overview

Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
22
Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants01:18

Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants

Oral anticoagulants are vital tools in preventing and treating blood clotting disorders. This diverse class of medications can be categorized as vitamin K antagonists, exemplified by warfarin, and direct thrombin inhibitors (DTIs), such as dabigatran, as well as factor Xa inhibitors, including rivaroxaban.
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
2.5K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
18
Drug toxicity: Idiosyncratic Reactions01:16

Drug toxicity: Idiosyncratic Reactions

Idiosyncratic drug reactions represent abnormal chemical responses that vary significantly among individuals, ranging from extreme sensitivity to low doses to insensitivity to high doses. These reactions often occur due to the drug's covalent binding with serum proteins, forming a foreign hapten that triggers an immunotoxicological response. The variability in drug reactions has a strong pharmacogenetic foundation, with genetic differences crucial in how individuals metabolize drugs. For...
31
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes01:28

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

Cytochrome P450 (CYP450) enzymes are a superfamily of heme-containing monooxygenases that play a pivotal role in Phase I drug metabolism by catalyzing oxidation and reduction reactions.These enzymes transform lipophilic xenobiotics into more hydrophilic metabolites, facilitating subsequent Phase II conjugation and eventual excretion. The CYP450 family is classified into families (e.g., CYP1–CYP3) and subfamilies (e.g., CYP2A, CYP2C), based on amino acid sequence homology.CYP450...
14