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Polymorphisms in the RAS and cardiac function.

Jop H van Berlo1, Yigal M Pinto

  • 1Department of Cardiology, University Hospital Maastricht, Cardiovascular Research Institute Maastricht, P. Debyelaan 25, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.

The International Journal of Biochemistry & Cell Biology
|April 5, 2003
PubMed
Summary
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The angiotensin converting enzyme (ACE) DD genotype shows a convincing association with left ventricular hypertrophy, unlike its refuted link to myocardial infarction. Further meta-analyses are needed for heart failure associations due to study limitations.

Area of Science:

  • Genetics and Cardiovascular Disease

Background:

  • Polymorphisms in the angiotensin converting enzyme (ACE) gene influence enzyme activity.
  • Numerous association studies have investigated the link between ACE gene variants and cardiovascular conditions, but methodological rigor varies.

Purpose of the Study:

  • To critically evaluate the association between ACE gene polymorphism and cardiovascular diseases, including myocardial infarction, left ventricular hypertrophy, and heart failure.
  • To highlight the need for stringent criteria and meta-analyses in genetic association studies.

Main Methods:

  • Review of existing association studies on ACE polymorphism and cardiovascular outcomes.
  • Analysis of study methodologies, sample sizes, and statistical significance.
  • Discussion of the biological plausibility of observed associations.

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Main Results:

  • The initial association between the ACE DD genotype and myocardial infarction risk was refuted by large-scale studies.
  • A more convincing association exists between the ACE DD genotype and left ventricular hypertrophy, particularly in untreated hypertensives (192% excess risk).
  • Associations with heart failure remain inconclusive due to heterogeneous study endpoints and small sample sizes, hindering meta-analysis.

Conclusions:

  • The ACE genotype plays a role in left ventricular growth, notably in athletes.
  • Methodological limitations in current association studies necessitate well-designed meta-analyses adhering to strict criteria (large sample size, statistical significance, biological relevance).
  • Further research with robust methodologies is crucial for clarifying the role of ACE polymorphism in heart failure.