Evidence map›Paper›PMID 23918469›Full record

ArticleThe AAPS journal2013

Functional analysis of novel polymorphisms in the human SLCO1A2 gene that encodes the transporter OATP1A2.

Fanfan Zhou, Jian Zheng, Ling Zhu, Andreas Jodal, Pei H Cui, Mark Wong, Howard Gurney, W Bret Church, Michael Murray

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The AAPS journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

20 citing papers in PubMed, 50 citations in OpenAlex.

  1. Effects of Green Tea Extract on Atorvastatin Pharmacokinetics in Healthy Volunteers.European journal of drug metabolism and pharmacokinetics · 2020
    Trial
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Impact of genetic variants in the solute carrier (Cancer drug resistance (Alhambra, Calif.) · 2024
    Review
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  9. Review
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  14. Article
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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

9 authors at 2 institutions in 2 countries.

Fanfan ZhouFaculty of Pharmacy, The University of Sydney, Sydney, NSW, 2006, Australia, fanfan.zhou@sydney.edu.au.
Jian Zheng
Ling Zhu
Andreas Jodal
Pei H Cui
Mark Wong
Howard Gurney
W Bret Church
Michael Murray
The University of Sydney · AUWestmead Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The solute carrier organic anion transporting polypeptide 1A2 (OATP1A2, SLCO1A2) is implicated in the cellular influx of a number of drugs. We identified five novel single nucleotide polymorphisms (SNPs) in coding exons of the SLCO1A2 gene in a cohort of subjects: G550A, G553A, G673A, A775C, and G862A, that encoded the OATP1A2 variants E184K, D185N, V255I, T259P, and D288N, respectively. The function and expression of these variant transporters were assessed in HEK-293 cells. We found that the novel variants, E184K, D185N, T259P, and D288N, were associated with impaired estrone-3-sulfate, imatinib, and methotrexate transport (∼20-50% of wild-type control); function was retained by OATP1A2-V255I. From biotinylation assays, the decreased function of these variants was due, at least in part, to impaired plasma membrane expression. The four loss-of-function variants were studied further using mutagenesis to produce variants that encode residues with different charges or steric properties. From immunoblotting, the replacement of negatively charged residues at amino acid positions 184 and 185 impaired membrane expression, while either a positive or negative charge at residue 288 supported the correct membrane targeting of OATP1A2. Replacement of T259 with bulky residues disrupted transporter stability. From molecular models, E184, D185, and D288 were located near several charged residues such that intramolecular ionic interactions may stabilize the transporter structure. Individuals who carry these novel SNPs in the SLCO1A2 gene may be at risk from impaired efficacy or enhanced toxicity during treatment with drugs that are substrates for OATP1A2.

Indexed as

Genetic CodeGenetic VariationHEK293 CellsHumansOrganic Anion TransportersPolymorphism, Single NucleotideOrganic Anion TransportersSLCO1A2 protein, human

Identifiers

PMID23918469
PMCPMC3787238
OpenAlexW2035401855

What OpenQuestion holds

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Registered trials

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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.