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

Authors: Faure-Delanef L; Baudin B; Bénéteau-Burnat B; Beaudoin JC; Giboudeau J; Cohen D

Abstract: 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.

Keywords: Adult; Aged; Aged, 80 and over; Alleles; Cardiovascular Diseases/enzymology/genetics; Female; Gene Deletion; Genotype; Humans; Kinetics; Male; Middle Aged; Peptidyl-Dipeptidase A/*blood/*genetics; Polymerase Chain Reaction; *Polymorphism, Genetic; Risk Factors
Journal: Clinical chemistry
Volume: 44
Issue: 10
Pages: 2083-7
Date: Oct. 7, 1998
PMID: 9761238
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Citation:

Faure-Delanef L, Baudin B, Bénéteau-Burnat B, Beaudoin JC, Giboudeau J, Cohen D (1998) Plasma concentration, kinetic constants, and gene polymorphism of angiotensin I-converting enzyme in centenarians. Clinical chemistry 44: 2083-7.


Lifespan Factors:
  • ACE angiotensin I converting enzyme (peptidyl-dipeptidase A) 1

  • Longevity Variant Associations (p-value):
  • rs1799752 (0.025)
  • rs4646994

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