Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

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

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...

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

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 isoenzymes,...

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

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...

Pharmacogenetics of Drug Metabolism: Overview

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...

Drug toxicity: Idiosyncratic Reactions

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...

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Direct oral anticoagulants vs warfarin in Asian vs non-Asian patients with atrial fibrillation: a patient-level meta-analysis from COMBINE AF.

European heart journal·2026

Same author

Bayesian Machine Learning Model Guiding Iterative, Personalized Anticoagulant Dosing Decision-Making: ENGAGE AF-TIMI 48 Trial Analysis.

JACC. Advances·2026

Same author

Systemic Embolic Events in Atrial Fibrillation: An Individual Patient Data Meta-analysis of 71 683 Participants Randomized to NOAC Versus Warfarin.

Circulation·2026

Same author

A polygenic risk score for peripheral artery disease and major adverse limb events.

European heart journal·2025

Same author

Prevalence of Undiagnosed OSA in Patients With All Patterns of Atrial Fibrillation.

JACC. Clinical electrophysiology·2025

Same author

Polygenic Risk Score for Coronary Artery Disease Across the Spectrum of Atherosclerotic Disease.

European journal of preventive cardiology·2025

Search research articles

Related Experiment Video

Updated: Jun 26, 2026

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform

Published on: May 10, 2024

Cytochrome p-450 polymorphisms and response to clopidogrel.

Jessica L Mega¹, Sandra L Close, Stephen D Wiviott

¹Thrombolysis in Myocardial Infarction Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. jmega@partners.org

The New England Journal of Medicine

|December 25, 2008

Summary

This summary is machine-generated.

Reduced-function CYP2C19 alleles significantly lower clopidogrel

More Related Videos

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

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

Published on: April 1, 2019

Related Experiment Videos

Last Updated: Jun 26, 2026

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform

Published on: May 10, 2024

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

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

Published on: April 1, 2019

Area of Science:

Pharmacogenomics
Cardiovascular Medicine
Drug Metabolism

Background:

Clopidogrel's antiplatelet effect relies on activation by cytochrome P-450 (CYP) enzymes.
Genetic variations in CYP enzymes, particularly CYP2C19, can impair clopidogrel activation.
Polymorphisms in CYP genes are common and may affect drug efficacy.

Purpose of the Study:

To investigate the association between CYP gene functional variants and clopidogrel's active metabolite levels.
To assess the impact of these genetic variants on platelet inhibition and cardiovascular outcomes in patients treated with clopidogrel.

Main Methods:

Genotyping for functional CYP variants in 162 healthy subjects and 1477 acute coronary syndrome patients.
Measurement of plasma clopidogrel active metabolite concentrations and platelet aggregation.
Analysis of cardiovascular outcomes (death, MI, stroke, stent thrombosis) in the TRITON-TIMI 38 trial.

Main Results:

CYP2C19 reduced-function allele carriers (30% of population) showed a 32.4% decrease in active metabolite levels and 9% less platelet inhibition.
In the TRITON-TIMI 38 cohort, carriers had a 53% increased risk of major adverse cardiovascular events (death, MI, stroke).
Carriers experienced a threefold higher risk of stent thrombosis compared to non-carriers.

Conclusions:

Reduced-function CYP2C19 alleles are linked to lower clopidogrel active metabolite levels and diminished platelet inhibition.
Individuals with these alleles face a significantly higher risk of adverse cardiovascular events, including stent thrombosis.
Genetic testing for CYP2C19 variants may inform clopidogrel therapy decisions.