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Why we are not able to find the coronary heart disease gene - apoE as an example

R Poledne1, J A Hubáček, V Staněk

  • 1Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic. rudolf.poledne@ikem.cz

Folia Biologica
|December 9, 2010
PubMed

Insights

Apolipoprotein E gene variants increase acute coronary syndrome risk, especially when traditional cardiovascular factors like smoking, diabetes, and hypertension are absent. This highlights gene-environment interactions in heart disease development.

Area of Science:

  • Cardiovascular Genetics
  • Atherosclerosis Research
  • Population Health Studies

Background:

  • The apolipoprotein E (APOE) gene is a key candidate gene for cardiovascular diseases.
  • Understanding APOE gene polymorphism's role in acute coronary syndrome (ACS) is crucial for risk stratification.
  • The influence of traditional cardiovascular risk factors on this association requires further investigation.

Purpose of the Study:

  • To investigate the association between apolipoprotein E gene polymorphism and acute coronary syndrome (ACS).
  • To determine if traditional cardiovascular risk factors modulate the relationship between APOE genotype and ACS manifestation.
  • To assess the impact of combined risk factors on ACS risk in a high-risk Czech population.

Main Methods:

  • Case-control study involving 1066 ACS patients and 1066 age-matched controls from Prague.
  • Genotyping for apolipoprotein E gene polymorphism.
  • Statistical analysis to compare genotype frequencies and calculate odds ratios, stratified by cardiovascular risk factors (smoking, diabetes, hypertension).

Main Results:

  • The disadvantageous E4+ genotype was significantly more frequent in ACS patients (22.38%) compared to controls (16.76%) (P < 0.01).
  • Odds ratios for ACS associated with the E4+ genotype increased progressively when patients were free of traditional risk factors: 1.35 (all), 1.48 (non-smokers), 1.53 (non-smokers + non-diabetics), and 1.71 (non-smokers + non-diabetics + normotensives).
  • The effect of APOE genotype on ACS risk is non-uniform and significantly modified by the presence or absence of cardiovascular risk factors.

Conclusions:

  • The apolipoprotein E genotype is associated with an increased risk of acute coronary syndrome in the studied Czech population.
  • Traditional cardiovascular risk factors, such as smoking, diabetes, and hypertension, significantly modify the impact of APOE gene polymorphism on ACS risk.
  • This suggests a complex interplay between genetic predisposition and environmental factors in the pathogenesis of atherosclerosis and ACS.

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