691
Views
18
CrossRef citations to date
0
Altmetric
Review

Clinical implications of genetic variation in carboxylesterase drug metabolism

, , &
Pages 131-142 | Received 03 Nov 2017, Accepted 19 Dec 2017, Published online: 04 Jan 2018

References

  • Satoh T, Hosokawa M. The mammalian carboxylesterases: from molecules to functions. Annu Rev Pharmacol Toxicol. 1998;38:257–288.
  • Hosokawa M, Furihata T, Yaginuma Y, et al. Genomic structure and transcriptional regulation of the rat, mouse, and human carboxylesterase genes. Drug Metab Rev. 2007;39(1):1–15.
  • Hosokawa M. Structure and catalytic properties of carboxylesterase isozymes involved in metabolic activation of prodrugs. Molecules. 2008;13(2):412–431.
  • Satoh T, Hosokawa M. Structure, function and regulation of carboxylesterases. Chem Biol Interact. 2006;162(3):195–211.
  • Laizure SC, Herring V, Hu Z, et al. The role of human carboxylesterases in drug metabolism: have we overlooked their importance? Pharmacotherapy. 2013;33(2):210–222.
  • Xu G, Zhang W, Ma MK, et al. Human carboxylesterase 2 is commonly expressed in tumor tissue and is correlated with activation of irinotecan. Clin Cancer Res. 2002;8(8):2605–2611.
  • Zhang W, Xu G, McLeod HL. Comprehensive evaluation of carboxylesterase-2 expression in normal human tissues using tissue array analysis. Appl Immunohistochem Mol Morphol. 2002;10(4):374–380.
  • Hatfield MJ, Tsurkan L, Garrett M, et al. Organ-specific carboxylesterase profiling identifies the small intestine and kidney as major contributors of activation of the anticancer prodrug CPT-11. Biochem Pharmacol. 2011;81(1):24–31.
  • Jones RD, Taylor AM, Tong EY, et al. Carboxylesterases are uniquely expressed among tissues and regulated by nuclear hormone receptors in the mouse. Drug Metab Dispos. 2013;41(1):40–49.
  • Lian J, Nelson R, Lehner R. Carboxylesterases in lipid metabolism: from mouse to human. Protein Cell. 2017.
  • Bencharit S, Edwards CC, Morton CL, et al. Multisite promiscuity in the processing of endogenous substrates by human carboxylesterase 1. J Mol Biol. 2006;363(1):201–214.
  • Imai T. Human carboxylesterase isozymes: catalytic properties and rational drug design. Drug Metab Pharmacokinet. 2006;21(3):173–185.
  • Imai T, Taketani M, Shii M, et al. Substrate specificity of carboxylesterase isozymes and their contribution to hydrolase activity in human liver and small intestine. Drug Metab Dispos. 2006;34(10):1734–1741.
  • Reilly PA, Lehr T, Haertter S, et al. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol. 2014;63(4):321–328.
  • Douxfils J, Mullier F, Dogné J-M. Dose tailoring of dabigatran etexilate: obvious or excessive? Expert Opin Drug Saf. 2015;14(8):1283–1289.
  • Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment. Diabetes. 2005;54(8):2430–2435.
  • Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol. 2007;49(14):1505–1516.
  • Erlinge D, Varenhorst C, Braun OO, et al. Patients with poor responsiveness to thienopyridine treatment or with diabetes have lower levels of circulating active metabolite, but their platelets respond normally to active metabolite added ex vivo. J Am Coll Cardiol. 2008;52(24):1968–1977.
  • Angiolillo DJ, Jakubowski JA, Ferreiro JL, et al. Impaired responsiveness to the platelet P2Y12 receptor antagonist clopidogrel in patients with type 2 diabetes and coronary artery disease. J Am Coll Cardiol. 2014;64(10):1005–1014.
  • Merali Z, Ross S, Paré G. The pharmacogenetics of carboxylesterases: CES1 and CES2 genetic variants and their clinical effect. Drug Metabol Drug Interact. 2014;29(3):143–151.
  • Rasmussen HB, Bjerre D, Linnet K, et al. Individualization of treatments with drugs metabolized by CES1: combining genetics and metabolomics. Pharmacogenomics. 2015;16(6):649–665.
  • Lam SW, van der Noort V, van der Straaten T, et al. Single-nucleotide polymorphisms in the genes of CES2, CDA and enzymatic activity of CDA for prediction of the efficacy of capecitabine-containing chemotherapy in patients with metastatic breast cancer. Pharmacol Res. 2017 Aug 18. pii: S1043-6618(17)30608-4. doi:10.1016/j.phrs.2017.08.005. [Epub ahead of print].
  • Oh J, Lee S, Lee H, et al. The novel carboxylesterase 1 variant c.662A>G may decrease the bioactivation of oseltamivir in humans. PLoS One. 2017;12(4):e0176320.
  • Pellicer M, García-González X, García MI, et al. Identification of new SNPs associated with severe toxicity to capecitabine. Pharmacol Res. 2017;120:133–137.
  • Stage C, Jürgens G, Guski LS, et al. The impact of CES1 genotypes on the pharmacokinetics of methylphenidate in healthy Danish subjects. Br J Clin Pharmacol. 2017;83(7):1506–1514.
  • Xiao F-Y, Luo J-Q, Liu M, et al. Effect of carboxylesterase 1 S75N on clopidogrel therapy among acute coronary syndrome patients. Sci Rep. 2017;7(1):7244.
  • Hamzic S, Kummer D, Milesi S, et al. Novel genetic variants in carboxylesterase 1 predict severe early-onset capecitabine-related toxicity. Clin Pharmacol Ther. 2017;102(5):796–804.
  • Wang X, Rida N, Shi J, et al. A comprehensive functional assessment of carboxylesterase 1 nonsynonymous polymorphisms. Drug Metab Dispos. 2017;45(11):1149–1155.
  • Rasmussen HB, Madsen MB, Lyauk YK, et al. Carboxylesterase 1A2 encoding gene with increased transcription and potential rapid drug metabolism in Asian populations. Drug Metab Pers Ther. 2017;32(3):163–168.
  • Stage C, Jürgens G, Guski LS, et al. The pharmacokinetics of enalapril in relation to CES1 genotype in healthy Danish volunteers. Basic Clin Pharmacol Toxicol. 2017;121(6):487–492.
  • Langmann T, Becker A, Aslanidis C, et al. Structural organization and characterization of the promoter region of a human carboxylesterase gene. Biochim Biophys Acta. 1997;1350(1):65–74.
  • Fukami T, Nakajima M, Maruichi T, et al. Structure and characterization of human carboxylesterase 1A1, 1A2, and 1A3 genes. Pharmacogenet Genomics. 2008;18(10):911–920.
  • Sanford JC, Wang X, Shi J, et al. Regulatory effects of genomic translocations at the human carboxylesterase-1 (CES1) gene locus. Pharmacogenet Genomics. 2016;26(5):197–207.
  • Zhu HJ, Langaee TY, Gong Y, et al. CES1P1 variant −816A>C is not associated with hepatic carboxylesterase 1 expression and activity or antihypertensive effect of trandolapril. Eur J Clin Pharmacol. 2016;72(6):681–687.
  • Tanimoto K, Kaneyasu M, Shimokuni T, et al. Human carboxylesterase 1A2 expressed from carboxylesterase 1A1 and 1A2 genes is a potent predictor of CPT-11 cytotoxicity in vitro. Pharmacogenet Genomics. 2007;17(1):1–10.
  • Rasmussen HB, Madsen MB, Hansen PR, et al. Nomenclature for alleles of the human carboxylesterase 1 gene. Pharmacogenet Genomics. 2017;27(2):78–80.
  • Sai K, Saito Y, Tatewaki N, et al. Association of carboxylesterase 1A genotypes with irinotecan pharmacokinetics in Japanese cancer patients. Br J Clin Pharmacol. 2010;70(2):222–233.
  • Zhu H-J, Markowitz JS. Carboxylesterase 1 (CES1) genetic polymorphisms and oseltamivir activation. Eur J Clin Pharmacol. 2013;69(3):733–734.
  • Hosokawa M, Furihata T, Yaginuma Y, et al. Structural organization and characterization of the regulatory element of the human carboxylesterase (CES1A1 and CES1A2) genes. Drug Metab Pharmacokinet. 2008;23(1):73–84.
  • Yoshimura M, Kimura T, Ishii M, et al. Functional polymorphisms in carboxylesterase1A2 (CES1A2) gene involves specific protein 1 (Sp1) binding sites. Biochem Biophys Res Commun. 2008;369(3):939–942.
  • Nelveg-Kristensen KE, Bie P, Ferrero L, et al. Pharmacodynamic impact of carboxylesterase 1 gene variants in patients with congestive heart failure treated with angiotensin-converting enzyme inhibitors. PLoS One. 2016;11(9):e0163341.
  • Wang X, Wang G, Shi J, et al. CES1 genetic variation affects the activation of angiotensin-converting enzyme inhibitors. Pharmacogenomics J. 2016;16(3):220–230.
  • Schwer H, Langmann T, Daig R, et al. Molecular cloning and characterization of a novel putative carboxylesterase, present in human intestine and liver. Biochem Biophys Res Commun. 1997;233(1):117–120.
  • Marsh S, Xiao M, Yu J, et al. Pharmacogenomic assessment of carboxylesterases 1 and 2. Genomics. 2004;84(4):661–668.
  • Wu MH, Chen P, Remo BF, et al. Characterization of multiple promoters in the human carboxylesterase 2 gene. Pharmacogenetics. 2003;13(7):425–435.
  • Wu MH, Chen P, Wu X, et al. Determination and analysis of single nucleotide polymorphisms and haplotype structure of the human carboxylesterase 2 gene. Pharmacogenetics. 2004;14(9):595–605.
  • Kim S-R, Sai K, Tanaka-Kagawa T, et al. Haplotypes and a novel defective allele of CES2 found in a Japanese population. Drug Metab Dispos. 2007;35(10):1865–1872.
  • Yamada S, Richardson K, Tang M, et al. Genetic variation in carboxylesterase genes and susceptibility to isoniazid-induced hepatotoxicity. Pharmacogenomics J. 2010;10(6):524–536.
  • Geshi E, Kimura T, Yoshimura M, et al. A single nucleotide polymorphism in the carboxylesterase gene is associated with the responsiveness to imidapril medication and the promoter activity. Hypertens Res. 2005;28(9):719–725.
  • Shi J, Wang X, Eyler RF, et al. Association of oseltamivir activation with gender and carboxylesterase 1 genetic polymorphisms. Basic Clin Pharmacol Toxicol. 2016;119(6):555–561.
  • Xie C, Ding X, Gao J, et al. The effects of CES1A2 A(−816)C and CYP2C19 loss-of-function polymorphisms on clopidogrel response variability among Chinese patients with coronary heart disease. Pharmacogenet Genomics. 2014;24(4):204–210.
  • Zhu H-J, Patrick KS, Yuan H-J, et al. Two CES1 gene mutations lead to dysfunctional carboxylesterase 1 activity in man: clinical significance and molecular basis. Am J Hum Genet. 2008;82(6):1241–1248.
  • Zhu H-J, Brinda B, Froehlich TE, et al. A discriminative analytical method for detection of CES1A1 and CES1A2/CES1A3 genetic variants. Pharmacogenet Genomics. 2012;22(3):215–218.
  • Cha Y-J, J H-E, Shin J-G, et al. Genetic polymorphisms of the carboxylesterase 1 (CES1) gene in a Korean population. Translational Clin Pharmacol. 2014;22(1):30–34.
  • Bruxel EM, Salatino-Oliveira A, Genro JP, et al. Association of a carboxylesterase 1 polymorphism with appetite reduction in children and adolescents with attention-deficit/hyperactivity disorder treated with methylphenidate. Pharmacogenomics J. 2013;13(5):476–480.
  • Saito S, Iida A, Sekine A, et al. Catalog of 680 variations among eight cytochrome p450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population. J Hum Genet. 2003;48(5):249–270.
  • Kim S-R, Nakamura T, Saito Y, et al. Twelve novel single nucleotide polymorphisms in the CES2 gene encoding human carboxylesterase 2 (hCE-2). Drug Metab Pharmacokinet. 2003;18(5):327–332.
  • Charasson V, Bellott R, Meynard D, et al. Pharmacogenetics of human carboxylesterase 2, an enzyme involved in the activation of irinotecan into SN-38. Clin Pharmacol Ther. 2004;76(6):528–535.
  • Mathijssen RH, Marsh S, Karlsson MO, et al. Irinotecan pathway genotype analysis to predict pharmacokinetics. Clin Cancer Res. 2003;9(9):3246–3253.
  • Kubo T, Kim S-R, Sai K, et al. Functional characterization of three naturally occurring single nucleotide polymorphisms in the CES2 gene encoding carboxylesterase 2 (HCE-2). Drug Metab Dispos. 2005;33(10):1482–1487.
  • Ribelles N, López-Siles J, Sánchez A, et al. A carboxylesterase 2 gene polymorphism as predictor of capecitabine on response and time to progression. Curr Drug Metab. 2008;9(4):336–343.
  • Fujiyama N, Miura M, Satoh S, et al. Influence of carboxylesterase 2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Xenobiotica. 2009;39(5):407–414.
  • Shi D, Yang J, Yang D, et al. Anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel. J Pharmacol Exp Ther. 2006;319(3):1477–1484.
  • Tarkiainen EK, Backman JT, Neuvonen M, et al. Carboxylesterase 1 polymorphism impairs oseltamivir bioactivation in humans. Clin Pharmacol Ther. 2012;92(1):68–71.
  • Zhu H-J, Markowitz JS. Activation of the antiviral prodrug oseltamivir is impaired by two newly identified carboxylesterase 1 variants. Drug Metab Dispos. 2009;37(2):264–267.
  • Nemoda Z, Angyal N, Tarnok Z, et al. Carboxylesterase 1 gene polymorphism and methylphenidate response in ADHD. Neuropharmacology. 2009;57(7–8):731–733.
  • Tarkiainen EK, Holmberg MT, Tornio A, et al. Carboxylesterase 1 c.428G>A single nucleotide variation increases the antiplatelet effects of clopidogrel by reducing its hydrolysis in humans. Clin Pharmacol Ther. 2015;97(6):650–658.
  • Investigators C-O, Mehta SR, Bassand J-P, et al. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med. 2010;363(10):930–942.
  • Tang M, Mukundan M, Yang J, et al. Antiplatelet agents aspirin and clopidogrel are hydrolyzed by distinct carboxylesterases, and clopidogrel is transesterificated in the presence of ethyl alcohol. J Pharmacol Exp Ther. 2006;319(3):1467–1476.
  • Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360(4):354–362.
  • Lewis JP, Horenstein RB, Ryan K, et al. The functional G143E variant of carboxylesterase 1 is associated with increased clopidogrel active metabolite levels and greater clopidogrel response. Pharmacogenet Genomics. 2013;23(1):1–8.
  • Zhao Z, Li X, Sun S, et al. Impact of genetic polymorphisms related to clopidogrel or acetylsalicylic acid pharmacology on clinical outcome in Chinese patients with symptomatic extracranial or intracranial stenosis. Eur J Clin Pharmacol. 2016;72(10):1195–1204.
  • Zou J-J, Chen S-L, Fan H-W, et al. CES1A −816C as a genetic marker to predict greater platelet clopidogrel response in patients with percutaneous coronary intervention. J Cardiovasc Pharmacol. 2014;63(2):178–183.
  • Zhu H-J, Wang X, Gawronski BE, et al. Carboxylesterase 1 as a determinant of clopidogrel metabolism and activation. J Pharmacol Exp Ther. 2013;344(3):665–672.
  • Bjerre D, Ferrero L, Madsen M, et al. Comment on Xie et al.: the effects of CES1A2 A(−816)C and CYP2C19 loss-of-function polymorphisms on clopidogrel response variability among Chinese patients with coronary heart disease. Pharmacogenet Genomics. 2015;25(3):147.
  • Laizure SC, Parker RB, Herring VL, et al. Identification of carboxylesterase-dependent dabigatran etexilate hydrolysis. Drug Metab Dispos. 2014;42(2):201–206.
  • Shi J, Wang X, Nguyen J-H, et al. Dabigatran etexilate activation is affected by the CES1 genetic polymorphism G143E (rs71647871) and gender. Biochem Pharmacol. 2016;119:76–84.
  • Paré G, Eriksson N, Lehr T, et al. Genetic determinants of dabigatran plasma levels and their relation to bleeding. Circulation. 2013;127(13):1404–1412.
  • Tarkiainen EK, Tornio A, Holmberg MT, et al. Effect of carboxylesterase 1 c.428G > A single nucleotide variation on the pharmacokinetics of quinapril and enalapril. Br J Clin Pharmacol. 2015;80(5):1131–1138.
  • Martín M, Martínez N, Ramos M, et al. Standard versus continuous administration of capecitabine in metastatic breast cancer (GEICAM/2009-05): a randomized, noninferiority phase II trial with a pharmacogenetic analysis. Oncologist. 2015;20(2):111–112.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.