Pharmacogenetic study of CES1 gene and enalapril efficacy

Enalapril is an orally administered angiotensin-converting enzyme inhibitor which is widely prescribed to treat hypertension, chronic kidney disease, and heart failure. It is an ester prodrug that needs to be activated by carboxylesterase 1 (CES1). CES1 is a hepatic hydrolase that in vivo biotransforms enalapril to its active form enalaprilat in order to produce its desired pharmacological impact. Several single nucleotide polymorphisms in CES1 gene are reported to alter the catalytic activity of CES1 enzyme and influence enalapril metabolism. G143E, L40T, G142E, G147C, Y170D, and R171C can completely block the enalapril metabolism. Some polymorphisms like Q169P, E220G, and D269fs do not completely block the CES1 function; however, they reduce the catalytic activity of CES1 enzyme. The prevalence of these polymorphisms is not the same among all populations which necessitate to consider the genetic panel of respective population before prescribing enalapril. These genetic variations are also responsible for interindividual variability of CES1 enzyme activity which ultimately affects the pharmacokinetics and pharmacodynamics of enalapril. The current review summarizes the CES1 polymorphisms which influence the enalapril metabolism and efficacy. The structure of CES1 catalytic domain and important amino acids impacting the catalytic activity of CES1 enzyme are also discussed. This review also highlights the importance of pharmacogenomics in personalized medicine.