Related Experiment Video

Updated: Aug 6, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

Drug transporter and metabolizing enzyme gene variants and nonnucleoside reverse-transcriptase inhibitor

Marylyn D Ritchie1, David W Haas, Alison A Motsinger

  • 1Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. marylyn.ritchie@vanderbilt.edu

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
|August 17, 2006
PubMed

Insights

Certain genetic variants, like MDR1, may reduce the risk of liver damage during antiretroviral therapy. An interaction between MDR1 and hepatitis B status accurately predicted this risk.

Area of Science:

  • Pharmacogenetics
  • Hepatology
  • Infectious Diseases

Background:

  • Hepatotoxicity is a significant concern during antiretroviral therapy (ART).
  • Specific genetic factors and viral co-infections may influence ART-induced liver injury.
  • Efavirenz and nevirapine are commonly used non-nucleoside reverse transcriptase inhibitors.

Purpose of the Study:

  • To investigate the association between genetic variants in MDR1, CYP2B6, and CYP3A4 and hepatotoxicity in patients on efavirenz- or nevirapine-based ART.
  • To identify genetic predictors of liver injury during antiretroviral treatment.

Main Methods:

  • Nested case-control study design.
  • Genotyping of MDR1, CYP2B6, and CYP3A4 gene variants.
  • Analysis of clinical data including ART regimen and hepatitis B surface antigen (HBsAg) status.

Main Results:

  • The MDR1 3435C-->T variant was associated with a decreased risk of hepatotoxicity (OR=0.254, P=.021).
  • A significant interaction between MDR1 genotype and HBsAg status was observed, predicting hepatotoxicity risk with 82% accuracy (P<.001).

Conclusions:

  • MDR1 genetic variations may play a protective role against ART-induced hepatotoxicity.
  • Combined assessment of MDR1 genotype and HBsAg status can improve prediction of liver injury risk in patients receiving efavirenz or nevirapine.

More Related Videos

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform06:21

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

Published on: May 10, 2024

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors05:46

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors

Published on: April 9, 2014

Related Concept Videos

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
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...
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

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...
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...
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 isoenzymes,...
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...