Evidence mapPaperPMID 19483665Full record

Trial reportPharmacogenetics and genomics2009

Effect of genetic variation in the organic cation transporter 2 on the renal elimination of metformin.

Ying Chen, Shuanglian Li, Chaline Brown, Stephen Cheatham, Richard A Castro, Maya K Leabman, Thomas J Urban, Ligong Chen, Sook Wah Yee, Ji Ha Choi and 4 more

Registry-linked trialOpen access · greenAbstract readClinical Trial
In one paragraph

Trial report in Pharmacogenetics and genomics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00187720 (Genetic Basis for Variation in the Renal Elimination of Metformin), which is not on this map. Cited by 93 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 1 pooled it
8.0field-weighted citation impact, top 2% 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.

NCT00187720 phase4completednot on this map

Genetic Basis for Variation in the Renal Elimination of Metformin

TypeinterventionalSponsorUniversity of California, San FranciscoRan2002 to 2008Enrolled23ConditionsOther Conditions That May Be A Focus of Clinical AttentionArmsMetformin
3 · Its place in the literature

Who cites it

93 citing papers in PubMed, 1 synthesis or guideline pooled it, 241 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Effects of Pregnancy on the Pharmacokinetics of Metformin.Drug metabolism and disposition: the biological fate of chemicals · 2020 · on this map
    Trial
  6. Trial
  7. Trial
  8. Trial
  9. Organic cation transporter variation and response to smoking cessation therapies.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2014
    Trial
  10. Trial
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Exome Sequence Data of Eight SLC Transporters Reveal ThatPharmaceuticals (Basel, Switzerland) · 2024
    Article
  17. Review
  18. Review
  19. Article
  20. Review

33 more citing papers are in PubMed but not listed here.

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

14 authors at 2 institutions in 2 countries.

Ying ChenDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California 94158, USA.
Shuanglian Li
Chaline Brown
Stephen Cheatham
Richard A Castro
Maya K Leabman
Thomas J Urban
Ligong Chen
Sook Wah Yee
Ji Ha Choi
Yong Huang
Claire M Brett
Esteban G Burchard
Kathleen M Giacomini
Bioengineering Center · RUUniversity of California, San Francisco · US

Funding

PHARMACOGENETICS OF MEMBRANE TRANSPORTERSU01GM061390 · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · 2000 to 2005
$17.7M
PHARMACOKINETICS &PHARMACODYNAMICS OF NICOTINER01DA002277 · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · 1985 to 2005
$1.7M
CLINICAL, PHARMACOLOGY, DRUG ACTION &PHARMACOKINETICST32GM007546 · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1985 to 2025
$1.4M
NCRR NIH HHS UL1 RR024131NIDA NIH HHS R01 DA002277NIGMS NIH HHS GM61390NIGMS NIH HHS T32 GM007546NIGMS NIH HHS T32 GM07546NIGMS NIH HHS U01 GM061390NIGMS NIH HHS U19 GM061390
6 · The paper itself

Abstract

objectiveThe goal of this study was to determine the effect of a genetic variant in the organic cation transporter 2 (OCT2), OCT2-808G/T, which results in an amino acid change, A270S, on the pharmacokinetics of the antidiabetic drug, metformin.

methodsThe uptake of metformin was performed in stably transfected HEK-293 cells expressing the empty vector (MOCK), the reference OCT2-808G, and the variant OCT2-808T. Healthy individuals with known OCT2 genotypes [14 homozygous for the OCT2 reference allele (808G/G) and nine heterozygous for the variant allele (808G/T, *3D)] were recruited to this study. Metformin concentrations in plasma and urine were measured by liquid chromatography-tandem mass spectrometry method. Creatinine levels were also measured in plasma and urine. Pharmacokinetic parameters were evaluated for both the groups.

resultsWe observed that in HEK-293 stably transfected cells, OCT2-808T had a greater capacity to transport metformin than did the reference OCT2. Metformin pharmacokinetics was characterized in 23 healthy volunteers of Caucasian and African-American ancestries. We observed that the renal clearance (CL(R)) and the net secretion (SrCL(R)) of metformin were significantly different between the volunteers heterozygous for the variant allele (808G/T), and the volunteers homozygous for the reference allele (808G/G) (P<0.005). Multivariate analysis revealed that OCT2 genotype was a significant predictor of CL(R) and SrCL(R) of metformin (P<0.01).

conclusionWe conclude that genetic variation in OCT2 plays an important role in the CL(R) and SrCL(R) of metformin in healthy volunteers.

Indexed as

Biological TransportCell LineGenetic LinkageHomozygoteHumansKidneyMetforminMutant ProteinsOrganic Cation Transporter 2Organic Cation Transport ProteinsPolymorphism, Single NucleotideTime FactorsMetforminMutant ProteinsOrganic Cation Transporter 2Organic Cation Transport ProteinsSLC22A2 protein, human

Identifiers

PMID19483665
PMCPMC3104496
OpenAlexW2168993879

What Socratic holds

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Registered trials

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 Socratic graph.