Carboxylesterase 1A2 encoding gene with increased transcription and potential rapid drug metabolism in Asian populations
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Henrik Berg Rasmussen
,
Majbritt Busk Madsen
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.
Acknowledgments
The project INDIvidualised drug therapy based on pharmacogenomics: focus on carboxylesterase 1, CES1 (INDICES) aims at developing strategies for individualized treatment with methylphenidate and angiotensin-converting enzyme inhibitors. It is supported by grant 10-092792/DSF from the Danish Council for Strategic Research, Programme Commission on Individuals, Disease and Society. Lisbeth Nymark Jørgensen and Gerda Demant Olesen are thanked for excellent technical assistance.
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.
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©2017 Walter de Gruyter GmbH, Berlin/Boston
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Artikel in diesem Heft
- Frontmatter
- Original Articles
- Genotyping and phenotyping of CYP2D6 and CYP3A isoenzymes in patients with alcohol use disorder: correlation with haloperidol plasma concentration
- Evaluation of the Ecstasy influence on tramadol and its main metabolite plasma concentration in rats
- Imatinib quantification in human serum with LC-MS3 as an effective way of protein kinase inhibitor analysis in biological matrices
- Preliminary study of the association between the elimination parameters of phenytoin and phenobarbital
- Effects of the genetic variants of organic cation transporters 1 and 3 on the pharmacokinetics of metformin in Jordanians
- Short Communications
- Carboxylesterase 1A2 encoding gene with increased transcription and potential rapid drug metabolism in Asian populations
- Need for pharmacogenetic studies on the prevalence of MTHFR mutations in Puerto Ricans and Hispanics
