Angiotensin-converting enzyme deletion allele is beneficial for the longevity of Europeans

Age (Dordr). 2012 Jun;34(3):583-95. doi: 10.1007/s11357-011-9270-0. Epub 2011 May 26.

Abstract

The human angiotensin converting enzyme (ACE) gene is one of the most investigated candidate genes for cardiovascular diseases (CVD), but the understanding of its role among the elderly is vague. Therefore, this study focuses at: (a) testing the association of ACE polymorphism with CVD risk factors among the elderly, and (b) detecting the possible unequal distribution of ACE genotypes between senescent and younger segments of the European populations. The association of ACE I/D polymorphism with CVD health status [hypertension (HT), obesity, dislypidemia] in 301 very old subjects (88.2 ± 5 years; F/M = 221/80) was tested by means of logistic regression analysis. The meta-analysis of D allele frequency in general vs. elderly (80+ years) groups was conducted using all publicly available data for European populations comprising both age cohorts. Multiple multinomial logistic regression revealed that within this elderly sample, age (younger olds, 80-90 years), female sex (OR = 3.13, 95% CI = 1.59-6.19), and elevated triglycerides (OR = 2.53, 95% CI = 1.29-4.95) were positively associated with HT, while ACE polymorphism was not. It was also established that the DD genotype was twice as high in 80+ cohort compared to general population of Croatia (p < 0.00001). This trend was confirmed by the meta-analysis that showed higher D allele frequencies in olds from nine of ten considered European populations (OR = 1.19, 95% CI = 1.08-1.31). The data in elderly cohort do not confirm previously reported role of ACE DD genotype to the development of HT. Moreover, meta-analysis indicated that ACE D allele has some selective advantage that contributes to longevity in majority of European populations.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Aging / genetics
  • Aging / metabolism*
  • Alleles
  • Cardiovascular Diseases / enzymology
  • Cardiovascular Diseases / ethnology
  • Cardiovascular Diseases / genetics*
  • Croatia / epidemiology
  • DNA / genetics*
  • Female
  • Follow-Up Studies
  • Gene Deletion*
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Incidence
  • Longevity / genetics*
  • Male
  • Peptidyl-Dipeptidase A / genetics*
  • Peptidyl-Dipeptidase A / metabolism
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Retrospective Studies
  • Risk Factors
  • Survival Rate / trends
  • White People / genetics*

Substances

  • DNA
  • Peptidyl-Dipeptidase A