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Apolipoprotein E allelic frequency in elderly smokers

E D Bowman¹, B Brömeke, W Lensing

¹Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-4255, USA.

American Journal of Medical Genetics

|March 21, 1998

Summary

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Genetic variations in apolipoprotein E (apoE) influence disease risk. In elderly smokers, the "at risk" apoE epsilon4 allele was less frequent, suggesting a survival effect against mortality in this group.

Area of Science:

Genetics
Human disease susceptibility
Metabolic activation

Background:

Susceptibility genes impact disease risk by altering metabolic activation of compounds.
Genetic polymorphisms can affect gene function and disease risk.
The apolipoprotein E (apoE) gene is crucial in cholesterol metabolism; the epsilon4 allele is linked to higher coronary artery disease risk and is underrepresented in the elderly.

Purpose of the Study:

To test the hypothesis that genetic polymorphisms related to mortality show decreased "at risk" allele frequency and increased "protective" allele frequency in elderly heavy smokers.
To investigate the association between apolipoprotein E (apoE) variant alleles and mortality in elderly smokers.

Main Methods:

Determined ApoE variant alleles in 81 elderly current smokers (mean age 72.5) and 82 younger autopsy donors (mean age 33).

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Analyzed allelic frequencies and correlated them with age and smoking pack-years.

Used chi-squared test for allelic frequency comparison and stratified analysis for age and genotype.

Main Results:

A borderline significant difference in apoE epsilon4 allelic frequencies was observed between elderly smokers (11%) and younger donors (18%) (P=0.05).
A significant difference in age was found when stratified by genotype in elderly smokers (P=0.03), with carriers of epsilon4 being younger on average.
No significant difference in pack-years of smoking was found across genotypes, indicating no selective survival effect based on smoking intensity.

Conclusions:

The findings confirm previous associations of altered apoE allelic frequencies in the elderly.
The study extends these findings to smokers, suggesting a potential survival effect of certain apoE genotypes in this population.
The underrepresentation of the at-risk apoE epsilon4 allele in elderly smokers may contribute to their survival despite increased mortality risks associated with smoking.