Plasma concentration, kinetic constants, and gene polymorphism of angiotensin I-converting enzyme in centenarians.
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.
Fondation Jean Dausset CEPH, Paris, France.
L
L
Faure-Delanef
B
B
Baudin
B
B
Bénéteau-Burnat
J C
JC
Beaudoin
J
J
Giboudeau
D
D
Cohen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors
D007703:Peptidyl-Dipeptidase A