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Drug Metabolism and Personalized Therapy

Official journal of the European Society of Pharmacogenomics and Personalised Therapy

Editor-in-Chief: Llerena, Adrián

Editorial Board: Benjeddou, Mongi / Chen, Bing / Dahl, Marja-Liisa / Devinsky, Ferdinand / Hirata, Rosario / Hubacek, Jaroslav A. / Ingelman-Sundberg, Magnus / Maitland-van der Zee, Anke-Hilse / Manolopoulos, Vangelis G. / Marc, Janja / Melichar, Bohuslav / Meyer, Urs A. / Nair, Sujit / Nofziger, Charity / Peiro, Ana / Sadee, Wolfgang / Salazar, Luis A. / Simmaco, Maurizio / Turpeinen, Miia / Schaik, Ron / Shin, Jae-Gook / Visvikis-Siest, Sophie / Zanger, Ulrich M.


CiteScore 2018: 1.01

SCImago Journal Rank (SJR) 2018: 0.277
Source Normalized Impact per Paper (SNIP) 2018: 0.446

Online
ISSN
2363-8915
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Volume 32, Issue 3

Issues

Carboxylesterase 1A2 encoding gene with increased transcription and potential rapid drug metabolism in Asian populations

Henrik Berg Rasmussen
  • Corresponding author
  • Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, 2 Boserupvej, Roskilde 4000, Denmark
  • Department of Science and Environment, Roskilde University, Roskilde, Denmark
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Majbritt Busk Madsen
  • Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark
  • Other articles by this author:
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/ Yassine Kamal Lyauk / Peter Riis Hansen / Timothy Hughes /
Published Online: 2017-08-14 | DOI: https://doi.org/10.1515/dmpt-2017-0012

Abstract

The carboxylesterase 1 gene (CES1) encodes a hydrolase implicated in the metabolism of commonly used drugs. CES1A2, a hybrid of CES1 and a CES1-like pseudogene, has a promoter that is weak in most individuals. However, some individuals harbor a promoter haplotype of this gene with two overlapping Sp1 sites that confer significantly increased transcription potentially leading to rapid drug metabolism. This CES1A2 haplotype has previously been reported to be common among Asians. Using polymerase chain reaction followed by sequencing, the present study examined variation in the promoter and 5′ untranslated region of CES1A2 in 120 Han Chinese and 120 Japanese people enrolled in the 1000 Genomes Project. We identified 11 single nucleotide variations, two of which were novel, in 145 of the individuals who were found to carry CES1A2. Alignment analysis indicated that the CES1A2 haplotype with the overlapping Sp1 sites has been generated by incorporation of a segment of CES1. All minor allele frequencies were equal to or below 0.022 and the frequencies of the minor haplotypes were up to 40-fold lower than previously reported, including that of the haplotype with the overlapping Sp1 sites. This information is novel and suggests that the pharmacogenetic relevance of CES1A2 is limited in Asians.

Keywords: Asian populations; carboxylesterase 1A2 gene; polymorphisms; promoter; transcriptional activity

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About the article

For members of the INDICES Consortium, see Section “List of all partners in the INDICES Consortium”.


Received: 2017-04-10

Accepted: 2017-06-27

Published Online: 2017-08-14

Published in Print: 2017-09-26


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: The Danish Council for Strategic Research, Programme Commission on Individuals, Disease and Society, grant 10-092792/DSF.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Drug Metabolism and Personalized Therapy, Volume 32, Issue 3, Pages 163–168, ISSN (Online) 2363-8915, ISSN (Print) 2363-8907, DOI: https://doi.org/10.1515/dmpt-2017-0012.

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