Evidence map›Paper›PMID 17352537›Full record

ArticlePLoS genetics2007

Function-altering SNPs in the human multidrug transporter gene ABCB1 identified using a Saccharomyces-based assay.

Hotcherl Jeong, Ira Herskowitz, Deanna L Kroetz, Jasper Rine

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.7field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 57 citations in OpenAlex.

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  10. Germline variants in cancer therapy.Cancer drug resistance (Alhambra, Calif.) · 2019
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Hotcherl JeongDepartment of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, United States of America.
Ira Herskowitz
Deanna L Kroetz
Jasper Rine
University of California, San Francisco · USUniversity of California, Berkeley · US

Funding

PHARMACOGENETICS OF MEMBRANE TRANSPORTERSU01GM061390 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GIACOMINI, KATHLEEN M · 2000 to 2009
$29.2M
Pharmacogenomics of Membrane TransportersU19GM061390 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SALI, ANDREJ · 2010 to 2014
$16.3M
GENETIC ANALYSIS OF THE GENES CONTROLLING A POSITIONR01GM031105 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI RINE, JASPER D · 1985 to 2020
$6.4M
GENETIC ANALYSIS OF GENES CONTROLLING A POSITION EFFECTR37GM031105 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI RINE, JASPER D · 1999 to 2008
$3.5M
NIGMS NIH HHS GM31105NIGMS NIH HHS GM61390NIGMS NIH HHS R01 GM031105NIGMS NIH HHS R37 GM031105NIGMS NIH HHS U01 GM061390NIGMS NIH HHS U19 GM061390
6 · The paper itself

Abstract

The human ABCB1 (MDR1)-encoded multidrug transporter P-glycoprotein (P-gp) plays a major role in disposition and efficacy of a broad range of drugs including anticancer agents. ABCB1 polymorphisms could therefore determine interindividual variability in resistance to these drugs. To test this hypothesis we developed a Saccharomyces-based assay for evaluating the functional significance of ABCB1 polymorphisms. The P-gp reference and nine variants carrying amino-acid-altering single nucleotide polymorphisms (SNPs) were tested on medium containing daunorubicin, doxorubicin, valinomycin, or actinomycin D, revealing SNPs that increased (M89T, L662R, R669C, and S1141T) or decreased (W1108R) drug resistance. The R669C allele's highly elevated resistance was compromised when in combination with W1108R. Protein level or subcellular location of each variant did not account for the observed phenotypes. The relative resistance profile of the variants differed with drug substrates. This study established a robust new methodology for identification of function-altering polymorphisms in human multidrug transporter genes, identified polymorphisms affecting P-gp function, and provided a step toward genotype-determined dosing of chemotherapeutics.

Indexed as

Antineoplastic AgentsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1Conserved SequenceDaunorubicinDoxorubicinDrug Resistance, FungalEvolution, MolecularGenetic Complementation TestHaplotypesHumansMutant ProteinsOrganic Anion TransportersPolymorphism, Single NucleotideProtein Structure, SecondaryProtein TransportABCB1 protein, humanAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1DaunorubicinDoxorubicinMutant ProteinsOrganic Anion Transporters

Identifiers

PMID17352537
PMCPMC1817653
OpenAlexW1995156193

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.