Related Experiment Video

Updated: May 5, 2026

A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis
04:30

A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis

Published on: May 14, 2013

27.4K

Genetic determinants of response to clopidogrel and cardiovascular events

Tabassome Simon1, Céline Verstuyft, Murielle Mary-Krause

  • 1Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, and Université Pierre et Marie Curie, Paris 06, France. tabassome.simon@sat.aphp.fr

The New England Journal of Medicine
|December 25, 2008
PubMed

Insights

Genetic variations in CYP2C19 increase cardiovascular event risk in acute myocardial infarction patients on clopidogrel. This risk is amplified in those undergoing percutaneous coronary intervention, highlighting pharmacogenetic importance.

Area of Science:

  • Cardiovascular Medicine
  • Pharmacogenetics
  • Genetics

Background:

  • Clopidogrel response varies due to pharmacogenetic factors affecting its antiplatelet activity.
  • The impact of these genetic factors on clinical outcomes post-acute myocardial infarction (AMI) remains unclear.

Purpose of the Study:

  • To investigate the association between genetic variants influencing clopidogrel metabolism and clinical outcomes in AMI patients.
  • To assess the risk of death, stroke, or myocardial infarction in relation to specific gene polymorphisms.

Main Methods:

  • 2208 AMI patients receiving clopidogrel were enrolled in a French registry.
  • Allelic variants in ABCB1, CYP3A5, CYP2C19, P2RY12, and ITGB3 genes were analyzed.
  • One-year follow-up assessed the risk of all-cause death, nonfatal stroke, or myocardial infarction.

Main Results:

  • No association was found between SNPs in CYP3A5, P2RY12, or ITGB3 and adverse outcomes.
  • Patients with two variant ABCB1 alleles (3435 TT) showed a higher cardiovascular event rate (15.5% vs. 10.7%).
  • Patients with two CYP2C19 loss-of-function alleles had a significantly higher event rate (21.5% vs. 13.3%), particularly those undergoing percutaneous coronary intervention (PCI).

Conclusions:

  • CYP2C19 loss-of-function alleles are linked to increased cardiovascular events in AMI patients treated with clopidogrel.
  • The heightened risk associated with CYP2C19 variants is especially pronounced in patients who have undergone PCI.
  • These findings underscore the clinical significance of pharmacogenetics in optimizing clopidogrel therapy for AMI patients.
Abstract

More Related Videos

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene07:00

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

Published on: April 1, 2019

11.7K
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

1.6K

Related Concept Videos

Principles of Pharmacogenetics: Types of Genetic Variants01:27

Principles of Pharmacogenetics: Types of Genetic Variants

The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
138
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...
159
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...
194
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...
81
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
121
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...
220