GENOTYPES WITH THE APOLIPOPROTEIN EPSILON-4 ALLELE ARE PREDICTORS OF CORONARY HEART-DISEASE MORTALITY IN A LONGITUDINAL-STUDY OF ELDERLY FINNISH MEN

Earlier we reported that allelic variation in the ene coding for apoli poprotein (apoE) is a significant predictor of variation in the risk o f coronary heart disease (CHD) death in a longitudinal study of elderl y Finnish men. Here we address the question: which of the apoE genotyp es confers the risk information in these men, and whether such informa tion persists after other CHD risk factors are considered? We followed two cohorts of elderly Finnish men aged 65 to 84 years, one in Easter n (n = 281) and the other in the Southwestern (n = 344) Finland for 5 years during which 26 (9.3%) of the men from the Eastern cohort and 40 (11.6%) of the men in the Southwestern cohort died from CHD. Baseline high density lipoprotein (HDL) cholesterol and (HDL cholesterol)(2) i n the Eastern cohort and age, and total and HDL cholesterol and smokin g status in the Southwestern cohort were significant predictors of CHD death (P < 0.05). The apoE genotypes were significant predictors in t he Southwestern cohort at P = 0.02 and in the Eastern cohort at P = 0. 18. In multivariable models, information about apoE genotypes improved the prediction at P = 0.10 level of statistical significance in both cohorts. When genotypes were considered separately, the epsilon 2/4 co mbined with the epsilon 4/4 in the Eastern cohort (odds ratio = 7.69, 95% CI = 1.67-35.52) and the epsilon 3/4 in the Southwestern cohort (o dds ratio = 2.44, 95% CI = 1.16-5.10) had sigificanctly greater odds o f CHD death compared to the common epsilon 3/3 genotype. We conclude t hat apoE genotypes confer risk information about CHD death in two coho rts of elderly Finnish men in a longitudinal study, and this informati on persists after adjustment for other CHD risk factors. Because diffe rent genotypes were predictors in these two cohorts, we further conclu de that the utility of a particular genotype as a predictor of CHD dea th in other populations may depend on the distribution of risk factor profiles at baseline, geographically defined environmental exposures, the CHD mortality history, and the evolutionary history of background genotypes in the population considered.