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

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.

The effect of milk proteins and curd on serum Angiotensin Converting Enzyme activity and lipid profile in Wistar rats

“…Similar variations in the standard deviation for the ACE activity have been reported in other animal and human studies as well 15,16 . On a rat model, standard deviation of 98.2 U/L was observed in a control group and 46.5 U/L in the diabetes group 15 , and in a human study a standard deviation of 36.8 U/L was observed where they suggested the variation may be due to the gene polymorphism of ANG I converting enzyme 16 . The cholesterol lowering activity seen in curd hydrolysates and whey treated group may be attributed to the lipolytic action of bacteria present in the fermented milk 1 .…”

Puzzling role of genetic risk factors in human longevity: “risk alleles” as pro-longevity variants

“…Overall, available evidence indicates that the ACE I/D polymorphism may influence multiple health traits, sometimes in opposite directions, also depending on age and interactions with other genes, such as APOE (Wang et al 2006 ). In case the deleterious and beneficial effects of ACE variants offset each other, or the beneficial effect prevails, the frequencies of ACE D allele (genetic risk factor for MI) may be similar or even higher in centenarians compared to younger controls, which is often observed in real data (Garatachea et al 2013 ; Zajc Petranovic et al 2012 ; Faure-Delanef et al 1998 ).…”

Role of angiotensin‐converting enzyme gene polymorphism in persistent pulmonary hypertension of the newborn

“…and II (12). Increased activity of ACE reported with its D allele (13,14) may drive excessive secretion of ATII and exaggerated pulmonary vascularization contributing to development of PPHN. Our hypothesis was that ACE DD genotype would increase the risk of PPHN and ⁄ or the severity of illness among term and near-term infants.…”

“…The human ACE gene contains a polymorphism of either an insertion (I) or a deletion (D) of a 287‐bp within intron 16 on chromosome 17, resulting in three genotypes: DD, DI and II (12). Increased activity of ACE reported with its D allele (13,14) may drive excessive secretion of ATII and exaggerated pulmonary vascularization contributing to development of PPHN. Our hypothesis was that ACE DD genotype would increase the risk of PPHN and/or the severity of illness among term and near‐term infants.…”