Related Experiment Video
Updated: Jun 17, 2026
08:42
Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport
Published on: November 27, 2016
Polymorphic variants in the human bile salt export pump (BSEP; ABCB11): functional characterization and
Richard H Ho1, Brenda F Leake, Dawn M Kilkenny
1Department of Pediatrics and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Pharmacogenetics and Genomics
|December 17, 2009
Summary
Genetic variations in the bile salt export pump (BSEP; ABCB11) can impair its function, potentially increasing susceptibility to liver disorders. Interindividual variability in BSEP expression also contributes to liver health differences.
Area of Science:
- Pharmacogenomics
- Hepatology
- Molecular Biology
Background:
- The bile salt export pump (BSEP; ABCB11) is crucial for bile acid transport and liver function.
- Genetic variations (polymorphisms) in ABCB11 can affect BSEP function and expression, potentially leading to liver disease.
Purpose of the Study:
- To identify and functionally characterize nonsynonymous single nucleotide polymorphisms (SNPs) in ABCB11.
- To assess interindividual variability in BSEP expression levels.
Main Methods:
- Identified 24 SNPs, including nine nonsynonymous variants, in ABCB11 from diverse healthy individuals.
- Functionally characterized wild-type and variant BSEP in vitro for taurocholate transport.
- Assessed BSEP expression using real-time mRNA, western blot, and immunofluorescence.
Main Results:
- Several rare BSEP variants (e.g., 616A>G, 1674G>C) significantly impaired taurocholate transport.
- The 3556G>A variant showed reduced cell surface expression.
- Wide interindividual variability in BSEP mRNA (19-fold) and protein (31-fold) expression was observed.
- The common 1331T>C variant was linked to reduced hepatic BSEP mRNA levels.
Conclusions:
- Functionally relevant polymorphisms in ABCB11 exist.
- These polymorphisms may predispose individuals to acquired liver disorders, such as drug-induced cholestasis.
More Related Videos
Related Concept Videos
01:16Pharmacogenetics 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...
01:31ABC Transporters: Exporter
ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
01:11Pharmacogenetics 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...
01:28Pharmacogenetics 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,...
01:29Pharmacogenetic 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...
01:27Principles 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...