Plasma concentration, kinetic constants, and gene polymorphism of angiotensin I-converting enzyme in centenarians

• Published in: Clinical chemistry (Baltimore, Md.) Md.), 1998-10, Vol.44 (10), p.2083-2087
• Main Authors: Faure-Delanef, Laurence, Baudin, Bruno, Beneteau-Burnat, Benedicte, Beaudoin, Jean-Christophe, Giboudeau, Jacqueline, Cohen, Daniel
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Alleles; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Cardiovascular Diseases - enzymology; Cardiovascular Diseases - genetics; Enzymes and enzyme inhibitors; Female; Fundamental and applied biological sciences. Psychology; Gene Deletion; Genotype; Humans; Hydrolases; Kinetics; Male; Middle Aged; Peptidyl-Dipeptidase A - blood; Peptidyl-Dipeptidase A - genetics; Polymerase Chain Reaction; Polymorphism, Genetic; Risk Factors
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1093/clinchem/44.10.2083

We have determined serum activity and kinetic constants of angiotensin I-converting enzyme (ACE), parallel to an insertion/deletion (I/D) polymorphism in its gene, in French centenarians and controls 20-70 years of age because this enzyme could have an impact on cardiovascular risk, and thus on longevity. Both the ACE D allele and ACE D/D genotype were more frequent in centenarians in comparison with controls, without sex-related differences nor significant correlation with a cardiovascular pathology. In centenarians, I/D polymorphism was correlated with circulating ACE activity (D/D genotype, 89.0 +/- 36.8 U/L; I/D genotype, 63.5 +/- 26.0 U/L; and I/I genotype, 55.1 +/- 39.4 U/L). The Michaelis constants for two substrates were identical whatever the genotype and were not different between centenarians and controls, i.e., 0.30 +/- 0.03 mmol/L for furylacryloyl-phenylalanyl-glycyl-glycine and 1.35 +/- 0.05 mmol/L for hippuryl-histidyl-leucine; for the latter, the optimal pH and activating concentration of chloride did not depend on I/D polymorphism. The maximal velocities with both substrates reflected the distribution of serum ACE activity as a function of the genotypes, in centenarians and in controls. In conclusion, plasma ACE activity is subject to a similar genotypic influence in centenarians as in adults 20-70 years of age; however, ACE itself appears to be functionally similar for each genotype. Furthermore, the D allele as well as the higher serum ACE activities associated with the D/D genotype cannot discriminate individuals at high risk for cardiovascular diseases, major causes of mortality before the age of 100 years.