Zhu_2016_Eur.J.Clin.Pharmacol_72_681

Reference

Title : CES1P1 variant -816A>C is not associated with hepatic carboxylesterase 1 expression and activity or antihypertensive effect of trandolapril - Zhu_2016_Eur.J.Clin.Pharmacol_72_681
Author(s) : Zhu HJ , Langaee TY , Gong Y , Wang X , Pepine CJ , Cooper-DeHoff RM , Johnson JA , Markowitz JS
Ref : European Journal of Clinical Pharmacology , 72 :681 , 2016
Abstract : PURPOSE: The 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.
METHODS: The -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).
RESULTS: Our 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.
CONCLUSIONS: We conclude that the -816A>C variant is not associated with interindividual variability in CES1 expression and activity or therapeutic response to ACEI prodrugs.
ESTHER : Zhu_2016_Eur.J.Clin.Pharmacol_72_681
PubMedSearch : Zhu_2016_Eur.J.Clin.Pharmacol_72_681
PubMedID: 26915813
Gene_locus related to this paper: human-CES1

Related information

Gene_locus related to this paper: human-CES1

Citations formats

Zhu HJ, Langaee TY, Gong Y, Wang X, Pepine CJ, Cooper-DeHoff RM, Johnson JA, Markowitz JS (2016)
CES1P1 variant -816A>C is not associated with hepatic carboxylesterase 1 expression and activity or antihypertensive effect of trandolapril
European Journal of Clinical Pharmacology 72 :681

Zhu HJ, Langaee TY, Gong Y, Wang X, Pepine CJ, Cooper-DeHoff RM, Johnson JA, Markowitz JS (2016)
European Journal of Clinical Pharmacology 72 :681