Related Experiment Video

Updated: Jul 4, 2026

Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases
14:57

Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases

Published on: October 10, 2020

Do glutathione-S-transferase polymorphisms influence response to intravenous cyclophosphamide therapy in idiopathic

Sheetal V Sharda1, Sanjeev Gulati, Gaurav Tripathi

  • 1Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, UP, India.

Pediatric Nephrology (Berlin, Germany)
|July 3, 2008
PubMed

Insights

Glutathione-S-transferase (GST) gene variations influence treatment outcomes in children with idiopathic nephrotic syndrome (INS). Specific GST genotypes predict response to cyclophosphamide (CP) therapy in steroid-sensitive cases.

Area of Science:

  • Genetics
  • Pediatrics
  • Pharmacogenomics

Background:

  • Idiopathic nephrotic syndrome (INS) response to cyclophosphamide (CP) varies significantly in children.
  • Glutathione-S-transferase (GST) gene polymorphisms are implicated in drug metabolism and response.
  • Predicting CP efficacy in pediatric INS remains a clinical challenge.

Purpose of the Study:

  • To investigate the association between GST gene polymorphisms (GSTM1, GSTT1, GSTP1) and treatment response to intravenous cyclophosphamide (IVCP) in children with INS.
  • To determine if specific GST genotypes correlate with remission rates in steroid-sensitive and steroid-resistant INS.

Main Methods:

  • Genotyping for GSTM1, GSTT1, and GSTP1 polymorphisms was performed in 74 children with INS.
  • Patients received IVCP therapy, and treatment response (remission) was assessed.
  • Statistical analysis correlated GST genotypes with IVCP response in steroid-sensitive and steroid-resistant subgroups.

Main Results:

  • Overall, 50% of children responded to CP therapy.
  • In steroid-sensitive INS, synergistic effects of GSTP1 Val105 polymorphism combined with GSTM1 and GSTT1 null genotypes were significantly associated with remission (p=0.013 and p=0.026).
  • No significant associations were found in the steroid-resistant INS group.

Conclusions:

  • GST gene polymorphisms, particularly combinations involving GSTP1 Val105 and null genotypes of GSTM1/GSTT1, are associated with CP response in children with steroid-sensitive INS.
  • These findings suggest that GST polymorphism may play a role in guiding CP therapy selection for pediatric INS.
  • Further research is warranted to validate these pharmacogenetic markers for clinical application in INS management.

More Related Videos

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS08:38

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS

Published on: November 8, 2015

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...
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...
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...
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...
Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation01:22

Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation

Glutathione, a tripeptide made up of glutamate, cysteine, and glycine, is a critical player in the detoxification of drugs and xenobiotics via a process known as glutathione conjugation or mercapturic acid formation. This phase II biotransformation reaction involves the covalent binding of glutathione to a drug or its metabolite, enhancing the compound's water solubility and enabling its excretion.
Several distinctive characteristics distinguish glutathione conjugation from other phase II...