↓ Skip to main content

Regulatory effects of genomic translocations at the human carboxylesterase-1 (CES1) gene locus

Overview of attention for article published in Pharmacogenetics and Genomics, May 2016
Altmetric Badge

About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (51st percentile)
  • Good Attention Score compared to outputs of the same age and source (78th percentile)

Mentioned by

twitter
5 X users

Citations

dimensions_citation
19 Dimensions

Readers on

mendeley
13 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Regulatory effects of genomic translocations at the human carboxylesterase-1 (CES1) gene locus
Published in
Pharmacogenetics and Genomics, May 2016
DOI 10.1097/fpc.0000000000000206
Pubmed ID
Authors

Jonathan C. Sanford, Xinwen Wang, Jian Shi, Elizabeth S. Barrie, Danxin Wang, Hao-Jie Zhu, Wolfgang Sadee

Abstract

CES1 encodes carboxylesterase-1, an important drug-metabolizing enzyme with high expression in the liver. Previous studies have reported a genomic translocation of the 5' region from the poorly expressed pseudogene CES1P1, to CES1, yielding the structural variant CES1VAR. The aim of this study was to characterize this translocation and its effect on CES1 expression in the human liver. Experiments were conducted in human liver tissues and cell culture (HepG2). The promoter and exon 1 of CES1 were sequenced by Sanger and Ion Torrent sequencing to identify gene translocations. The effects of CES1 5'UTRs on mRNA and protein expression were assessed by quantitative real-time PCR, allelic ratio mRNA analysis by primer extension (SNaPshot), quantitative targeted proteomics, and luciferase reporter gene assays. Sequencing of CES1 identified two translocations: first, CES1VAR (17% minor allele frequency) comprising the 5'UTR, exon 1, and part of intron 1. A second shorter translocation, CES1SVAR, was observed excluding exon 1 and intron 1 regions (<0.01% minor allele frequency). CES1VAR is associated with 2.6-fold decreased CES1 mRNA and ∼1.35-fold lower allelic mRNA. Luciferase reporter constructs showed that CES1VAR decreases luciferase activity 1.5-fold, whereas CES1SVAR slightly increases activity. CES1VAR was not associated with CES1 protein expression or metabolism of the CES1 substrates enalapril, clopidogrel, or methylphenidate in the liver. The frequent translocation variant CES1VAR reduces mRNA expression of CES1 in the liver by ∼30%, but protein expression and metabolizing activity in the liver were not detectably altered - possibly because of variable CES1 expression masking small allelic effects. Whether drug therapies are affected by CES1VAR will require further in-vivo studies.

X Demographics

X Demographics

The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 13 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 4 31%
Professor 2 15%
Student > Bachelor 1 8%
Student > Master 1 8%
Student > Doctoral Student 1 8%
Other 0 0%
Unknown 4 31%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 3 23%
Agricultural and Biological Sciences 3 23%
Biochemistry, Genetics and Molecular Biology 2 15%
Psychology 1 8%
Medicine and Dentistry 1 8%
Other 0 0%
Unknown 3 23%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 May 2016.
All research outputs
#14,599,900
of 25,373,627 outputs
Outputs from Pharmacogenetics and Genomics
#696
of 1,236 outputs
Outputs of similar age
#148,607
of 311,866 outputs
Outputs of similar age from Pharmacogenetics and Genomics
#4
of 19 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,236 research outputs from this source. They receive a mean Attention Score of 3.8. This one is in the 43rd percentile – i.e., 43% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 311,866 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.
We're also able to compare this research output to 19 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 78% of its contemporaries.