Prospective evaluation of the angiotensin-converting enzyme insertion/deletion polymorphism and the risk of stroke

Circulation. 1999 Jan 26;99(3):340-3. doi: 10.1161/01.cir.99.3.340.

Abstract

Background: The D/I polymorphism of the ACE gene has been studied in relation to a variety of cardiovascular disorders, including stroke. A number of small studies have been conducted, with inconsistent results. We investigated the association between ACE genotype and the incidence of stroke in a large, prospective, matched case-control sample from the Physicians' Health Study.

Methods and results: In the Physicians' Health Study, 348 subjects who had been apparently healthy at enrollment suffered a stroke during 12 years of follow-up, as determined from medical records and autopsy. A total of 348 cases were matched by age, time of randomization, and smoking habit to an equal number of controls (who had remained free of stroke). The D/I polymorphism was determined by polymerase chain reaction. Data were analyzed for the entire nested case-control sample, and also among a subgroup without a history of hypertension or diabetes mellitus, considered to be at low conventional risk (207 cases and 280 controls). All observed genotype frequencies were in Hardy-Weinberg equilibrium. The relative risk associated with the D allele was 1.11 (95% CI, 0.90 to 1.37; P=0.35), assuming an additive model in the matched analysis. Additional analyses assuming dominant or recessive effects of the D allele, as well as the analysis after stratification for low-risk status, showed no material as a statistically significant association.

Conclusions: The results of this large, prospective study indicate that the ACE D/I gene polymorphism is not associated with subsequent risk of stroke.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Antioxidants / administration & dosage
  • Aspirin / administration & dosage
  • Case-Control Studies
  • Cerebrovascular Disorders / drug therapy
  • Cerebrovascular Disorders / epidemiology
  • Cerebrovascular Disorders / genetics*
  • Gene Deletion*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Myocardium / enzymology
  • Peptidyl-Dipeptidase A / genetics*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Polymorphism, Genetic*
  • Prospective Studies
  • Risk Factors
  • beta Carotene / administration & dosage

Substances

  • Antioxidants
  • Platelet Aggregation Inhibitors
  • beta Carotene
  • Peptidyl-Dipeptidase A
  • Aspirin