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OBJECTIVE: To investigate the relationship between the apolipoprotein E (APOE) gene and the risk of mortality in normal weight, overweight and obese individuals. METHODS AND RESULTS: In a population-based study of 7,983 individuals aged 55 years and older, we compared the risks of all-cause and coronary heart disease (CHD) mortality by APOE genotype, both overall and in subgroups defined by body mass index (BMI). We found significant evidence for interaction between APOE and BMI in relation to total cholesterol (p=0.04) and HDL cholesterol (p<0.001). Overall, APOE*2 carriers showed a decreased risk of all-cause mortality. Analyses within BMI strata showed a beneficial effect of APOE*2 only in normal weight persons (adjusted hazard ratio (HR) 0.7[95% CI 0.5-0.9]). APOE*2 was not associated with a lower risk of all-cause mortality in overweight or obese persons. The effect of APOE*2 in normal weight individuals tended to be due to the risk of CHD mortality (adjusted HR 0.5 [95% CI 0.2-1.2]). CONCLUSION: The APOE*2 allele confers a lower risk of all-cause mortality only to normal weight individuals.

Original publication




Journal article


European journal of epidemiology

Publication Date





135 - 142


Department of Epidemiology & Biostatistics, Erasmus MC University Medical Center Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.


Humans, Coronary Disease, Genetic Predisposition to Disease, Body Weight, Apolipoproteins E, Body Mass Index, Incidence, Mortality, Risk, Longitudinal Studies, Safety Management, Genotype, Aged, Middle Aged, Netherlands, Female, Male, Kaplan-Meier Estimate