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Mortality differences by APOE genotype estimated from demographic synthesis.

Douglas C Ewbank1

  • 1Population Studies Center, University of Pennsylvania, Philadelphia 19104, USA. ewbank@pop.upenn.edu

Genetic Epidemiology
|January 15, 2002
PubMed
Summary

The apolipoprotein E (APOE) 4 allele increases mortality risk for heart disease and Alzheimer's. However, its impact lessens significantly in individuals over 100 years old.

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Area of Science:

  • Genetics
  • Demography
  • Epidemiology

Background:

  • The apolipoprotein E (APOE) 4 allele is linked to higher risks of ischemic heart disease and Alzheimer's disease.
  • APOE 4 allele frequency decreases with age, suggesting an association with increased mortality.
  • Understanding the age-specific mortality risks associated with APOE genotypes is crucial for public health.

Purpose of the Study:

  • To extend demographic models for estimating relative mortality risks based on gene frequencies across age groups.
  • To synthesize gene frequency data with cohort study mortality data by genotype.
  • To quantify the association between APOE genotype and mortality risk across different ages.

Main Methods:

  • Developed and applied an extended demographic model combining gene frequencies and cohort mortality data.

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  • Analyzed data from Denmark, Finland, France, Italy, Sweden, and the United States.
  • Calculated relative mortality risks for different APOE genotypes (e.g., 3/4, 4/4, 2/3) compared to the 3/3 genotype.

    • Main Results:

    • Near age 50, the APOE 3/4 genotype showed a 1.34-fold increased mortality risk (95% CI 1.18-1.67) compared to 3/3.
    • The APOE 4/4 genotype exhibited a relative risk of 1.81, while the 2/3 genotype was protective with a relative risk of 0.84 (0.68-0.93).
    • These genotype-specific mortality risks converged towards 1.0 at older ages, with minimal variation in mortality over age 100.

    Conclusions:

    • APOE genotype influences mortality risk, particularly in mid-life, but this association diminishes significantly in centenarians.
    • The demographic modeling approach effectively integrates genetic and mortality data to assess population-level health risks.
    • Findings suggest that while APOE 4 poses risks, its impact on survival is limited at extreme ages.