Evidence map›Paper›PMID 26915813›Full record

Trial reportEuropean journal of clinical pharmacology2016

CES1P1 variant -816A>C is not associated with hepatic carboxylesterase 1 expression and activity or antihypertensive effect of trandolapril.

Hao-Jie Zhu, Taimour Y Langaee, Yan Gong, Xinwen Wang, Carl J Pepine, Rhonda M Cooper-DeHoff, Julie A Johnson, John S Markowitz

Open access · greenAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

5 citing papers in PubMed, 14 citations in OpenAlex.

  1. Trial
  2. Review
  3. Carboxylesterase 1 and Precision Pharmacotherapy: Pharmacogenetics and Nongenetic Regulators.Drug metabolism and disposition: the biological fate of chemicals · 2020
    Review
  4. Article
  5. Article
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

8 authors at 2 institutions in 1 country.

Hao-Jie ZhuDepartment of Clinical Pharmacy, University of Michigan, Ann Arbor, MI, USA.
Taimour Y LangaeeDepartment of Pharmacotherapy and Translational Research, University of Florida, 1600 SW Archer Road, RM PG-23, Gainesville, FL, 32610-0486, USA.
Yan GongDepartment of Pharmacotherapy and Translational Research, University of Florida, 1600 SW Archer Road, RM PG-23, Gainesville, FL, 32610-0486, USA.
Xinwen WangDepartment of Clinical Pharmacy, University of Michigan, Ann Arbor, MI, USA.
Carl J PepineDivision of Cardiovascular Medicine, Department of Medicine, University of Florida, Gainesville, FL, USA.
Rhonda M Cooper-DeHoffDepartment of Pharmacotherapy and Translational Research, University of Florida, 1600 SW Archer Road, RM PG-23, Gainesville, FL, 32610-0486, USA.
Julie A JohnsonDepartment of Pharmacotherapy and Translational Research, University of Florida, 1600 SW Archer Road, RM PG-23, Gainesville, FL, 32610-0486, USA.
John S MarkowitzDepartment of Pharmacotherapy and Translational Research, University of Florida, 1600 SW Archer Road, RM PG-23, Gainesville, FL, 32610-0486, USA. jmarkowitz@cop.ufl.edu.
University of Florida · USUniversity of Michigan–Ann Arbor · US

Funding

Michigan Institute for Clinical and Health Research (MICHR)UL1TR002240 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LUMENG, JULIE C, MASHOUR, GEORGE ALEXANDER · 2017 to 2022
$54.9M
Michigan Institute for Clinical and Health Research (MCHR)UL1TR000433 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MASHOUR, GEORGE ALEXANDER · 2012 to 2016
$49.9M
Pharmacogenomic Evaluation of Antihypertensive ResponsesU01GM074492 · NIGMS · UNIVERSITY OF FLORIDA · PI JOHNSON, JULIE A. · 2005 to 2014
$20.7M
CES1 variants as determinant of ACE inhibitor activation: a healthy volunteer studyR21AG048500 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZHU, HAOJIE · 2015 to 2016
$426k
NCATS NIH HHS UL1 TR000433NCATS NIH HHS UL1 TR002240NIA NIH HHS R21 AG048500NIGMS NIH HHS U01 GM074492
6 · The paper itself

Abstract

purposeThe majority of angiotensin-converting enzyme inhibitors (ACEIs) are synthesized as ester prodrugs that must be converted to their active forms in vivo in order to exert therapeutic effects. Hepatic carboxylesterase 1 (CES1) is the primary enzyme responsible for the bioactivation of ACEI prodrugs in humans. The genetic variant -816A>C (rs3785161) is a common variant located in the promoter region of the CES1P1 gene. Previous studies report conflicting results with regard to the association of this variant and therapeutic outcomes of CES1 substrate drugs. The purpose of this study was to determine the effect of the variant -816A>C on the activation of the ACEI prodrug trandolapril in human livers and the blood pressure (BP)-lowering effect of trandolapril in hypertensive patients.

methodsThe -816A>C genotypes and CES1 expression and activity on trandolapril activation were determined in 100 individual human liver samples. Furthermore, the association of the -816A>C variant and the BP lowering effect of trandolapril was evaluated in hypertensive patients who participated in the International Verapamil SR Trandolapril Study (INVEST).

resultsOur in vitro study demonstrated that hepatic CES1 expression and activity did not differ among different -816A>C genotypes. Moreover, we were unable to identify a clinical association between the BP lowering effects of trandolapril and -816A>C genotypes.

conclusionsWe conclude that the -816A>C variant is not associated with interindividual variability in CES1 expression and activity or therapeutic response to ACEI prodrugs.

Indexed as

AdultAgedAged, 80 and overAngiotensin-Converting Enzyme InhibitorsAntihypertensive AgentsCarboxylic Ester HydrolasesFemaleHumansIndolesLiverMaleMiddle AgedPolymorphism, Single NucleotideYoung AdultAngiotensin-Converting Enzyme InhibitorsAntihypertensive AgentsCarboxylic Ester HydrolasesCES1P1 protein, humanCES1 protein, humanIndolestrandolaprilAngiotensin-converting enzyme inhibitorsCarboxylesterase 1 (CES1)Drug metabolismHypertensionPharmacogenomicsTrandolapril

Identifiers

PMID26915813
PMCPMC4865408
OpenAlexW2282635932

What OpenQuestion holds

Textmetadata
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.