Abstract
Many individuals possess an allele of the angiotensin I-converting enzyme (ACE) gene, which contains an extra 287-kb fragment in intron 16 (Rigat et al. 1992). Although the functionality of this fragment is at present unclear, the absence (deletion, D) or presence (insertion, I) of this fragment appears to be related to both the amount and activity of circulating ACE. This paper reports the possible polymorphic response of ACE to the ACE inhibitor enalaprilat in 54 normal Chinese subjects that is independent of the I/D polymorphism. The kinetics of ACE inhibition with enalaprilat was studied in serum from 54 normal Chinese subjects. Enalaprilat appK i ranged between 0.46 and 2.16 nM. An antimode was observed at 1.4 nM. Four subjects could be characterized as being poor responders to enalaprilat.
Similar content being viewed by others
References
Cambien F, Poirier O, Lecerf L, Evans A, Cambou J-P, Arveiler D, Luc G, Bard J-M, Bara L, Ricard S, Tiret L, Amouyel P, Alhenc-Gelas F, Soubrier F (1992) Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 359:641–4
Friedland J, Silverstein E (1976) A sensitive fluorimetric assay for serum angiotensin-converting enzyme. Am J Clin Pathol 66:416–23
Higashimori K, Zhao Y, Higaki J, Kamitani A, Katsuya T, Nakura J, Miki T, Mikami H, Ogihara T (1993) Association analysis of a polymorphism of the angiotensin converting enzyme gene with essential hypertension in the Japanese population. Biochem Biophys Res Commun 191:399–404
Hubert C, Houot A-M, Corvol P, Soubrier F (1991) Structure of the angiotensin I-converting enzyme gene: two alternate promoters correspond to evolutionary steps of a duplicated gene. J Biol Chem 266:15377–15383
Kaplan HR, Taylor DG, Olson SC, Andrews LK (1989) Quinapril — a preclinical review of the pharmacology, pharmacokinetics, and toxicology. Angiology 40:335–350
Lee EJD (1994a) Population genetics of the angiotensin-converting enzyme in Chinese. Br J Clin Pharmacol 37:212–214
Lee EJD (1994b) The angiotensin I-converting enzyme genetic polymorphism is associated with altered substrate affinity. Pharmacogenetics 4:101–103
Morris BJ, Zee RYL, Ying LH, Griffiths LR (1993) Independent, marked associations of alleles of the insulin receptor and dipeptidyl carboxypeptidase genes with essential hypertension. Clin Sci 85:189–195
Petrillo EW Jr, Ondetti MA (1982) Angiotensin-converting enzyme inhibitors: medicinal chemistry and biological actions. Med Res Rev 2:1–41
Rigat B, Hubert C, Corvol P, Soubrier F (1992) PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme (DCP1) (dipeptidyl carboxypeptidase 1). Nucleic Acids Res 20:1433
Shapiro R, Riordan JF (1984) Inhibition of angiotensin converting enzyme: mechanism and substrate dependence. Biochemistry 23:5225–5233
Tiret L, Rigat B, Visvikis S, Breda C, Corvol P, Cambien F, Soubrier F (1992) Evidence, from combined segregation and linkage analysis, that the variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet 1:197–205
Wei L, Alhenc-Gelas F, Corvol P, Clauser E (1991) The two homologous domains of human angiotensin I-converting enzyme are both catalytically active. J. Biol Chem 266:9002–9008
Zee RYL, Lou Y-K, Griffiths LR, Morris BJ (1992) Association of a polymorphism of the angiotensin I-converting enzyme gene with essential hypertension. Biochem Biophys Res Commun 184:9–15
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lee, E.J.D. Polymorphic inhibition of human angiotensin I-converting enzyme by enalaprilat. Eur J Clin Pharmacol 49, 173–175 (1995). https://doi.org/10.1007/BF00192376
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00192376