Evidence map›Paper›PMID 21649730›Full record

ArticleJournal of gastroenterology and hepatology2011

Functional characterization of genetic variants in the apical sodium-dependent bile acid transporter (ASBT; SLC10A2).

Richard H Ho, Brenda F Leake, Brad L Urquhart, Jamie C Gregor, Paul A Dawson, Richard B Kim

Abstract read
In one paragraph

Article in Journal of gastroenterology and hepatology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 27% 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, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. [Bile Acid Diarrhea].The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi · 2024
    Review
  9. New Developments in Bile Acid Diarrhea.Gastroenterology & hepatology · 2023
    Article
  10. Article
  11. Contributions of bile acids to gastrointestinal physiology as receptor agonists and modifiers of ion channels.American journal of physiology. Gastrointestinal and liver physiology · 2022
    Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Bile acid dysregulation, gut dysbiosis, and gastrointestinal cancer.Experimental biology and medicine (Maywood, N.J.) · 2014
    Review
  19. Cystic fibrosis related liver disease--another black box in hepatology.International journal of molecular sciences · 2014
    Review
  20. Review
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

6 authors at 3 institutions in 2 countries.

Richard H HoDepartment of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Brenda F Leake
Brad L Urquhart
Jamie C Gregor
Paul A Dawson
Richard B Kim
Western University · CAVanderbilt University Medical Center · USWake Forest University · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STACIE B DUSETZINA · 1995 to 2026
$172.8M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
Vanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ALVIN C POWERS · 2012 to 2026
$29.3M
TRANSGENIC MOUSE/ ES CELL SHARES RESOURCESP60DK020593 · NIDDK · VANDERBILT UNIVERSITY · PI POWERS, ALVIN C · 1986 to 2011
$28.1M
Shop Module CoreP30EY008126 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI David J. Calkins · 1989 to 2026
$19.6M
THREE-TIERED PREVENTION MODEL TO BETTER SERVE ALL STUDENP30HD015052 · NICHD · VANDERBILT UNIVERSITY · PI HARRELL, FRANK E. · 1985 to 2014
$18.6M
ILEAL BILE ACID TRANSPORTER METABOLISM AND REGULATIONR01DK047987 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI DAWSON, PAUL A · 2000 to 2021
$6.8M
HEPATIC DRUG TRANSPORTERS IN DRUG DISPOSITIONR01GM054724 · NIGMS · VANDERBILT UNIVERSITY · PI RODEN, DAN M · 1998 to 2006
$2.2M
cAMP Signaling in Sympathoadrenal Cell DevelopmentR01DK059367 · NIDDK · PURDUE UNIVERSITY WEST LAFAYETTE · PI ANDRISANI, OURANIA M. · 2002 to 2005
$1.2M
MRP2, BSEP, and BCRP Transporter Polymorphisms and Chemotherapy DispositionK08GM081363 · NIGMS · VANDERBILT UNIVERSITY · PI HO, RICHARD HSINSHIN · 2007 to 2011
$706k
ILEAL BILE ACID TRANSPORTER METABOLISM AND REGULATIONR29DK047987 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI DAWSON, PAUL A · 1994 to 1998
–
HEPATIC DRUG TRANSPORTERS IN DRUG DISPOSITIONR55GM054724 · NIGMS · VANDERBILT UNIVERSITY · PI KIM, RICHARD B · 1997 to 1997
–
NCI NIH HHS CA68485NCI NIH HHS P30 CA068485NEI NIH HHS EY08126NEI NIH HHS P30 EY008126NICHD NIH HHS HD15052NICHD NIH HHS P30 HD015052NIDDK NIH HHS DK20593NIDDK NIH HHS DK47987NIDDK NIH HHS DK58404NIDDK NIH HHS DK59367NIDDK NIH HHS P30 DK020593NIDDK NIH HHS P30 DK058404NIDDK NIH HHS R01 DK047987NIDDK NIH HHS R01 DK059367NIDDK NIH HHS R29 DK047987NIGMS NIH HHS GM54724NIGMS NIH HHS GM81363NIGMS NIH HHS K08 GM081363NIGMS NIH HHS R01 GM054724
6 · The paper itself

Abstract

BACKGROUND AND

aimThe major transporter responsible for bile acid uptake from the intestinal lumen is the apical sodium-dependent bile acid transporter (ASBT, SLC10A2). Analysis of the SLC10A2 gene has identified a variety of sequence variants including coding region single nucleotide polymorphisms (SNPs) that may influence bile acid homeostasis/intestinal function. In this study, we systematically characterized the effect of coding SNPs on SLC10A2 protein expression and bile acid transport activity.

methodsSingle nucleotide polymorphisms in SLC10A2 from genomic DNA of ethnically-defined healthy individuals were identified using a polymerase chain reaction (PCR)-based temperature gradient capillary electrophoresis (TGCE) system. A heterologous gene expression system was used to assess transport activity of SLC10A2 nonsynonymous variants and missense mutations. Total and cell surface protein expression of wild-type and variant ASBT was assessed by Western blot analysis and immunofluorescence confocal microscopy. Expression of ASBT mRNA and protein was also measured in human intestinal samples.

resultsThe studies revealed two nonsynonymous SNPs, 292G>A and 431G>A, with partially impaired in vitro taurocholate transport. A novel variant, 790A>G, was also shown to exhibit near complete loss of taurocholate transport, similar to the previously identified ASBT missense mutations. Examination of ASBT protein expression revealed no significant differences in expression or trafficking to the cell surface among variants versus wild-type ASBT. Analysis of ASBT mRNA and protein expression in human intestinal samples revealed modest intersubject variability.

conclusionsGenome sequencing and in vitro studies reveal the presence of multiple functionally relevant variants in SLC10A2 that may influence bile acid homeostasis and physiology.

Indexed as

Bile Acids and SaltsCell MembraneGene FrequencyGenetic VariationHomeostasisHumansIntestinal MucosaOrganic Anion Transporters, Sodium-DependentPolymorphism, Single NucleotideSymportersBile Acids and SaltsOrganic Anion Transporters, Sodium-Dependentsodium-bile acid cotransporterSymporters

Identifiers

PMID21649730
PMCPMC3170668
OpenAlexW1544418983

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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.