The DD-ACE genotype and cardiovascular disease

Pharmacogenomics. 2000 May;1(2):153-67. doi: 10.1517/14622416.1.2.153.


The renin-angiotensin-aldosterone system (RAS) plays a pivotal role in the cardiovascular system, and the therapeutic agents which interact with this pathway have a significant impact in both heart failure and following myocardial infarction (MI). Polymorphisms within the genes controlling this enzyme system may also contribute to the pathogenesis of cardiovascular disease. Over the last decade an association between a polymorphism of the angiotensin converting enzyme (ACE) gene (called the DD-ACE polymorphism) and phenotypic expression of cardiovascular disease, namely MI, has been reported. Since then, several small case-controlled studies have confirmed an association with manifestations of ischaemic heart disease or various other cardiac end points. However, in a large prospective study the ACE gene was found to confer no appreciable risk. This review article considers the evidence that links polymorphisms of the ACE gene with cardiovascular disease. The Medline database (1990 - 2000) was searched using the keywords myocardial infarction, ischaemic heart disease, angiotensin converting enzyme, polymorphisms (a search of the reference citations of relevant articles was also performed), and clinical studies on cardiovascular disease related to the ACE genotype were selected. Taken together, the available evidence supports the notion that the DD-ACE genotype adversely influences specific cardiovascular diseases, but appears to do so in specific geographical areas and in particular patient subgroups. It is not yet known whether it does this through an interaction with other genes or by as yet unexplained biochemical mechanisms. However, the impact of the DD-ACE genotype appears to be small and its clinical manifestations rather heterogeneous. This finding is not in contrast to the overall impact of the renin-angiotensin system in cardiovascular disease, given the fact that the ACE enzyme is only one component in the renin-angiotensin cascade and that one genetic variant cannot be expected to contribute more than a minor individual impact in genetically complex multifactorial cardiovascular disease.

Publication types

  • Review

MeSH terms

  • Alleles
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Animals
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / enzymology*
  • Cardiovascular Diseases / genetics*
  • Humans
  • Isoenzymes / genetics
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Genetic / genetics


  • Angiotensin-Converting Enzyme Inhibitors
  • Isoenzymes
  • Peptidyl-Dipeptidase A