Angiotensin converting enzyme gene, smoking and mortality in a population-based study

Eur J Clin Invest. 2005 Jul;35(7):444-9. doi: 10.1111/j.1365-2362.2005.01515.x.


Background: The genetic and environmental risk factors, which may influence longevity and mortality, have received much attention during more than one decade. One of the major risks for mortality is cardiovascular disease and the renin angiotensin system (RAS) plays a major role in maintaining blood pressure homeostasis. In this system, the Angiotensin Converting Enzyme (ACE) is one of the key regulators and has been studied in relation to cardiovascular disease and mortality. We aimed to evaluate if the ACE I/D polymorphism is related to total mortality in the elderly.

Materials and methods: Some 6968 elderly individuals from the Rotterdam study were genotyped for this polymorphism. Smoking was studied as a possible covariable or effect modifier. To examine the effect of the ACE genotype on mortality, a Cox proportional hazards model was fitted.

Results: Our results show an increased risk of total mortality in subjects with age at death below 65 years carriers of the DD genotype (HR 1.8, 95% CI 1.1-2.9, P = 0.016). This association was significant in total and cause specific mortality only in those who smoke (P-value < 0.001 for gene-age interaction). Our findings suggest that the ACE gene is rather associated with early mortality than with late.

Conclusions: Individuals who carry the DD genotype appear to be susceptible to early mortality if they smoke, suggesting a possible interaction between smoking and the ACE gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / genetics
  • Cardiovascular Diseases / mortality
  • Female
  • Follow-Up Studies
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mortality*
  • Neoplasms / mortality
  • Netherlands / epidemiology
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Genetic*
  • Proportional Hazards Models
  • Sex Factors
  • Smoking / genetics*
  • Smoking / mortality
  • Survival Analysis


  • Peptidyl-Dipeptidase A