Evidence map›Paper›PMID 24853734›Full record

ArticleClinical pharmacology and therapeutics2014

Genetic variants in transcription factors are associated with the pharmacokinetics and pharmacodynamics of metformin.

S Goswami, S W Yee, S Stocker, J D Mosley, M Kubo, R Castro, J A Mefford, C Wen, X Liang, J Witte and 8 more

Erratum issuedAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical pharmacology and therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 40 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 4 pooled it
4.0field-weighted citation impact, top 5% 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

40 citing papers in PubMed, 4 syntheses or guidelines pooled it, 64 citations in OpenAlex.

  1. Influence of Solute Carrier Family 22 Member 1 (Current diabetes reviews · 2024
    Pooled it
  2. Pooled it
  3. Pooled it
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  5. Trial
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  9. Review
  10. Review
  11. CPMKG: a condition-based knowledge graph for precision medicine.Database : the journal of biological databases and curation · 2024
    Article
  12. Article
  13. Review
  14. Review
  15. Biphasic effect of metformin on human cardiac energetics.Translational research : the journal of laboratory and clinical medicine · 2021
    Article
  16. Article
  17. Article
  18. Pharmacogenetics of Type 2 Diabetes-Progress and Prospects.International journal of molecular sciences · 2020
    Review
  19. Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 6 institutions in 2 countries.

S GoswamiDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
S W YeeDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
S StockerDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
J D MosleyDepartment of Pharmacology and Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
M KuboCenter of Genomic Medicine, RIKEN, Yokohama City, Japan.
R CastroDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
J A MeffordDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
C WenDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
X LiangDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
J WitteDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
C BrettDepartment of Anesthesiology, University of California, San Francisco, San Francisco, California, USA.
S MaedaCenter of Genomic Medicine, RIKEN, Yokohama City, Japan.
M D SimpsonMarshfield Clinic Research Foundation, Marshfield, Wisconsin, USA.
M M HeddersonDivision of Research, Kaiser Permanente Northern California, Oakland, California, USA.
R L DavisCenter for Health Research Southeast, Kaiser Permanente Georgia, Atlanta, Georgia, USA.
D M RodenDepartment of Pharmacology and Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
K M GiacominiDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
R M SavicDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
University of California, San Francisco · USRIKEN Center for Integrative Medical Sciences · JPVanderbilt University Medical Center · USKaiser Permanente · USMarshfield Clinic · USSoutheast Health District · US

Funding

UCSF Liver Core CenterP30DK026743 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Holger Willenbring · 1986 to 2026
$30.7M
PHARMACOGENETICS OF MEMBRANE TRANSPORTERSU01GM061390 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GIACOMINI, KATHLEEN M · 2000 to 2009
$29.2M
Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRUMMEL, MATTHEW F · 2003 to 2019
$21.8M
Pharmacogenomics of Membrane TransportersU19GM061390 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KWOK, PUI-YAN · 2010 to 2014
$16.3M
PHARMACEUTICAL SCIENCES AND PHARMACOGENOMICST32GM007175 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, KROETZ, DEANNA L · 1985 to 2021
$7.1M
American Heart Association-American Stroke Association 16FTF30130005NIDDK NIH HHS P30 DK026743NIDDK NIH HHS P30 DK063720NIGMS NIH HHS GM61390NIGMS NIH HHS T32 GM007175NIGMS NIH HHS U01 GM061390NIGMS NIH HHS U19 GM061390
6 · The paper itself

Abstract

One-third of type 2 diabetes patients do not respond to metformin. Genetic variants in metformin transporters have been extensively studied as a likely contributor to this high failure rate. Here, we investigate, for the first time, the effect of genetic variants in transcription factors on metformin pharmacokinetics (PK) and response. Overall, 546 patients and healthy volunteers contributed their genome-wide, pharmacokinetic (235 subjects), and HbA1c data (440 patients) for this analysis. Five variants in specificity protein 1 (SP1), a transcription factor that modulates the expression of metformin transporters, were associated with changes in treatment HbA1c (P < 0.01) and metformin secretory clearance (P < 0.05). Population pharmacokinetic modeling further confirmed a 24% reduction in apparent clearance in homozygous carriers of one such variant, rs784888. Genetic variants in other transcription factors, peroxisome proliferator-activated receptor-α and hepatocyte nuclear factor 4-α, were significantly associated with HbA1c change only. Overall, our study highlights the importance of genetic variants in transcription factors as modulators of metformin PK and response.

Indexed as

PharmacogeneticsPolymorphism, Single NucleotideAdultAgedAged, 80 and overBiomarkersDiabetes Mellitus, Type 2FemaleGenome-Wide Association StudyGlycated HemoglobinHepatocyte Nuclear Factor 4HomozygoteHumansHypoglycemic AgentsMaleMetforminBiomarkersGlycated Hemoglobinhemoglobin A1c protein, humanHepatocyte Nuclear Factor 4HNF4A protein, humanHypoglycemic AgentsMetforminPPAR alphaSp1 Transcription FactorTranscription Factors

Identifiers

PMID24853734
PMCPMC4171106
OpenAlexW2115846266

What OpenQuestion holds

Texttitle and abstract
LicenceTDM
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.