title: The pharmacogenetics of carboxylesterases: CES1 and CES2 genetic variants and their clinical effect.
abstract: Human carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2) are serine esterases responsible for the hydrolysis of ester and amide bonds present in a number of pharmaceutical products. Several common genetic variants of the CES1 and CES2 genes have been shown to influence drug metabolism and clinical outcomes. Polymorphisms of the CES1 gene have been reported to affect the metabolism of dabigatran etexilate, methylphenidate, oseltamivir, imidapril, and clopidogrel, whereas variants of the CES2 gene have been found to affect aspirin and irinotecan. Although the findings of these studies may be preliminary, they demonstrate the potential clinical utility of CES polymorphisms; however, more research is required, especially with respect to CES2. In this review, we outline the functional, molecular, and genetic properties of CES1 and CES2, and highlight recent studies that have shown relations between CES1 and CES2 variants and contemporary pharmacotherapy.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Merali
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ross
authors.forename: Guillaume
authors.initials: G
authors.lastname: Paré
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism; D000998:Antiviral Agents / Q000378:metabolism; D001241:Aspirin / Q000378:metabolism; D001562:Benzimidazoles / Q000378:metabolism; D002166:Camptothecin / Q000031:analogs & derivatives / Q000378:metabolism; D043182:Carboxylesterase / Q000235:genetics*; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000378:metabolism; D000077144:Clopidogrel; D000069604:Dabigatran; D065427:Factor Xa Inhibitors / Q000378:metabolism; D005838:Genotype; D006801:Humans; D048289:Imidazolidines / Q000378:metabolism; D000077146:Irinotecan; D007527:Isoenzymes / Q000737:chemistry / Q000502:physiology; D008774:Methylphenidate / Q000378:metabolism; D053139:Oseltamivir / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism; D011110:Polymorphism, Genetic; D011725:Pyridines / Q000378:metabolism; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000998:Antiviral Agents; D001562:Benzimidazoles; D000697:Central Nervous System Stimulants; D065427:Factor Xa Inhibitors; D048289:Imidazolidines; D007527:Isoenzymes; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D008774:Methylphenidate; D053139:Oseltamivir; D000077146:Irinotecan; D000077144:Clopidogrel; C065166:imidapril; D002265:Carboxylic Ester Hydrolases; C474609:CES1 protein, human; C517204:CES2 protein, human; D043182:Carboxylesterase; D000069604:Dabigatran; D013988:Ticlopidine; D001241:Aspirin; D002166:Camptothecin