Evidence map›Paper›PMID 24945780›Full record

ArticlePharmacogenetics and genomics2014

The influence of the CYP2C19*10 allele on clopidogrel activation and CYP2C19*2 genotyping.

Taimour Y Langaee, Hao-Jie Zhu, Xinwen Wang, Nihal El Rouby, John S Markowitz, Joyce A Goldstein, Julie A Johnson

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Pharmacogenetics and genomics, 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 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

6 citing papers in PubMed, 14 citations in OpenAlex.

  1. Cannabis Pharmacogenomics: A Path to Personalized Medicine.Current issues in molecular biology · 2023
    Review
  2. Pharmacogenomics Informs Cardiovascular Pharmacotherapy.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  3. Evaluation ofPharmacogenomics and personalized medicine · 2021
    Article
  4. Article
  5. Article
  6. Article
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

7 authors at 5 institutions in 2 countries.

Taimour Y LangaeeaDepartment of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida bDepartment of Clinical, Social, and Administrative Sciences, University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA cKey Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, People's Republic of China dNational Institute of Environmental Health Science, Research Triangle Park, North Carolina, USA.
Hao-Jie Zhu
Xinwen Wang
Nihal El Rouby
John S Markowitz
Joyce A Goldstein
Julie A Johnson
University of Florida · USUniversity of Michigan–Ann Arbor · USAmerican Association of Colleges of Pharmacy · USAnn Arbor Center for Independent Living · USTriangle · US

Funding

Pharmacogenomic Evaluation of Antihypertensive ResponsesU01GM074492 · NIGMS · UNIVERSITY OF FLORIDA · PI COOPER-DEHOFF, RHONDA M, JOHNSON, JULIE A. · 2005 to 2014
$20.7M
Sparking Advancements in Genomic MedicineU01HG007269 · NHGRI · UNIVERSITY OF FLORIDA · PI CAVALLARI, LARISA HUMMA, JOHNSON, JULIE A. · 2013 to 2024
$17.0M
UF CLINICAL AND TRANSLATIONAL SCIENCE AWARDUL1RR029890 · NCRR · UNIVERSITY OF FLORIDA · PI NELSON, DAVID R · 2009 to 2011
$14.4M
UF Clinical and Translational Science AwardUL1TR000064 · NCATS · UNIVERSITY OF FLORIDA · PI NELSON, DAVID R · 2012 to 2014
$12.2M
Drug Metabolizing Enzymes In Humans And Animal ModelsZIAES021024 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI GOLDSTEIN, JOYCE · 2009 to 2015
$11.0M
EFFECTS OF ENVIRONMENTAL CHEMICALS ON DRUG-METABOLIZING ENZYMESZ01ES021024 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI GOLDSTEIN, JOYCE · 1985 to 2008
$3.4M
Genetic Variants of Human Carboxylesterase 1 Influence the Activation and AntivirR21AI096345 · NIAID · UNIVERSITY OF FLORIDA · PI MARKOWITZ, JOHN S · 2011 to 2012
$403k
Intramural NIH HHS Z01 ES021024Intramural NIH HHS ZIA ES021024NCATS NIH HHS UL1 TR000064NCATS NIH HHS UL1TR000064NCRR NIH HHS UL1 RR029890NCRR NIH HHS UL1RR029890-03S3NHGRI NIH HHS U01 HG007269NIAID NIH HHS 1R21AI096345NIAID NIH HHS R21 AI096345NIEHS NIH HHS ES021024-32NIGMS NIH HHS U01 GM074492
6 · The paper itself

Abstract

BACKGROUND/

objectivesThe polymorphic hepatic enzyme CYP2C19 catalyzes the metabolism of clinically important drugs such as clopidogrel, proton-pump inhibitors, and others and clinical pharmacogenetic testing for clopidogrel is increasingly common. The CYP2C19*10 single-nucleotide polymorphism (SNP) is located 1 bp upstream the CYP2C19*2 SNP. Despite the low frequency of the CYP2C19*10 allele, its impact on metabolism of CYP2C19 substrates and CYP2C19*2 genotyping makes it an important SNP to consider for pharmacogenetic testing of CYP2C19. However, the effect of the CYP2C19*10 allele on clopidogrel metabolism has not been explored to date.

methodsWe measured the enzymatic activity of the CYP2C19.10 protein against clopidogrel. DNA samples from two clinical studies were genotyped for CYP2C19*2 and *10 by pyrosequencing genotyping method.

resultsThe catalytic activity of CYP2C19.10 in the biotransformation of clopidogrel and 2-oxo-clopidogrel was significantly decreased relative to the wild-type CYP2C19.1B. We also reported that the CYP2C19*10 SNP interferes with the CYP2C19*2 TaqMan genotyping assay, resulting in miscalling of CYP2C19*10/*2 as CYP2C19*2/*2.

conclusionsOur data provide evidence that CYP2C19.10 variant partially metabolizes clopidogrel and 2-oxo-clopidogrel, and the presence of CYP2C19*10 allele affects the CY2C19*2 TaqMan genotyping assay and results in misclassification of CYP2C19*10/*2 as CYP2C19*2/*2.

Indexed as

AllelesAryl Hydrocarbon HydroxylasesCatalysisChromatography, LiquidClopidogrelCytochrome P-450 CYP2C19GenotypeHumansKineticsMephenytoinOmeprazolePharmacogeneticsPolymorphism, Single NucleotideSequence Analysis, DNATandem Mass SpectrometryTiclopidine2-oxo-clopidogrelAryl Hydrocarbon HydroxylasesClopidogrelCYP2C19 protein, humanCytochrome P-450 CYP2C19MephenytoinOmeprazoleTiclopidine

Identifiers

PMID24945780
PMCPMC4090277
OpenAlexW1998680343

What OpenQuestion holds

Textmetadata
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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.