Reappraisal of the Genetic Diversity and Pharmacogenetic Assessment of CES1

Abstract

The CES1 gene encodes a hydrolase that metabolizes important drugs. Variants generated by exchange of segments with CES1P1 complicate genotyping of CES1. Using a highly specific procedure we examined DNA samples from 200 Caucasians and identified 46 single nucleotide variants (SNVs) in CES1 and 21 SNVs in CES1A2, a hybrid composed of CES1 and CES1P1. Several of these SNVs were novel. The frequencies of SNVs with a potential functional impact were below 0.02 suggesting limited pharmacogenetic potential for CES1 genotyping. In silico PCR revealed that the majority of the primer pairs for amplification of CES1 or CES1A2 in three previous studies lacked specificity, which partially explains a limited overlap with our findings.

Key words::

• CES1
• genetic diversity
• pharmacogenetic assessment
• single nucleotide variants
• structural variants

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/full/10.2217/pgs-2017-0052

Acknowledgements

The project INDICES (INDIvidualised drug therapy based on pharmacogenomics: focus on carboxylesterase 1, CES1) aims at developing strategies for individualized treatment with methylphenidate and angiotensin-converting enzyme inhibitors. Lisbeth Nymark J⊘rgensen and Gerda Demant Olesen are thanked for their excellent technical assistance.

Financial & competing interests disclosure

The project INDICES is supported by grant 10–092792/DSF from the Danish Council for Strategic Research, Programme Commission on Individuals, Disease and Society. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The project INDICES is supported by grant 10–092792/DSF from the Danish Council for Strategic Research, Programme Commission on Individuals, Disease and Society. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.