Related Experiment Video

Updated: Jun 14, 2026

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
09:34

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

Published on: April 4, 2018

MDR1 C2005T polymorphism changes substrate specificity

Lijuan Liu1, Lan Fan, Xiangdong Peng

  • 1Institute of Clinical Pharmacology, Central South University, Changsha, China.

Cancer Chemotherapy and Pharmacology
|March 24, 2010
PubMed
Abstract

Insights

The MDR1 C2005T polymorphism impacts how cells transport substances and respond to certain chemotherapy drugs. This genetic variation may affect drug effectiveness and how the body processes P-glycoprotein substrates.

Area of Science:

  • Pharmacogenomics
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • The MDR1 gene encodes P-glycoprotein (P-gp), a crucial efflux transporter involved in drug resistance.
  • Genetic variations, such as the MDR1 C2005T polymorphism, can potentially alter P-gp function and influence treatment outcomes.

Purpose of the Study:

  • To investigate the functional consequences of the MDR1 C2005T polymorphism on P-gp efflux activity.
  • To determine the effect of this polymorphism on cellular sensitivity to various anticancer agents.

Main Methods:

  • Quantitative real-time PCR and immunoblotting were used to measure MDR1 mRNA and protein expression.
  • Confocal microscopy assessed P-glycoprotein localization.
  • Cell cytotoxicity assays (MTT) and Rh123 permeability assays evaluated drug sensitivity and efflux activity.

Main Results:

  • The MDR1 C2005T polymorphism did not alter MDR1 expression levels or P-gp plasma membrane trafficking.
  • Cells with the MDR1 C2005T polymorphism showed altered sensitivity to paclitaxel and etoposide.
  • A significant increase in Rhodamine 123 (Rh123) efflux transport was observed in cells with the MDR1 C2005T polymorphism.

Conclusions:

  • The MDR1 C2005T polymorphism modifies the transepithelial permeability of P-gp substrates like Rh123.
  • This genetic variation influences cellular response to specific cytotoxic drugs, potentially impacting drug disposition and therapeutic efficacy.

More Related Videos

High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism Genotyping: An Innovative Tool for Alzheimer's Disease Gene Susceptibility Assessment07:26

High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism Genotyping: An Innovative Tool for Alzheimer's Disease Gene Susceptibility Assessment

Published on: July 18, 2017

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...
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...
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...
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,...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
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...