APOE POLYMORPHISM AND PREDISPOSITION TO CORONARY HEART-DISEASE IN YOUTHS OF DIFFERENT EUROPEAN POPULATIONS - THE EARS STUDY

The European Atherosclerosis Research Study was based on the compariso n of offspring having a paternal history of premature myocardial infar ction with age- and sex-matched control subjects. Case (n = 635) and c ontrol (n = 1259) subjects aged 18 through 26 years were recruited fro m 14 universities of 11 European countries. The allele distributions o f apolipoprotein (apo) E polymorphism differed between populations, wi th a clear-cut gradient for allele epsilon 4 frequency decreasing from 0.18 in Finland to 0.11 in the south of Europe, following the gradien t of coronary heart disease mortality rates. The association of apoE p olymorphism with plasma total cholesterol, low-density lipoprotein cho lesterol, apoB, and apoE levels was consistent with the now well-ident ified effects of epsilon 2 and epsilon 4 alleles on these traits. Both epsilon 2 and epsilon 4 alleles equally increased the level of trigly cerides, and epsilon 2 had a lowering effect on lipoprotein(a) concent ration. There were also weak effects of epsilon 2 and epsilon 4 on hig h-density lipoprotein cholesterol, apoA-I, and apoA-I-containing lipop rotein levels that paralleled those on apoE levels. The main finding o f this study was the significant association of the apoE polymorphism with a paternal history of myocardial infarction. The association was consistent across regions, except in the south. When excluding this re gion, the population-adjusted odds ratios by reference to phenotype E3 /3 were estimated as 0.23, 0.61, 0.78, 1.16, and 1.33 for E2/2, E3/2, E4/2, E4/3, and E4/4, respectively. The apoE locus largely explained t he case/control difference of apoB level. These results provide a body of evidence that apoE polymorphism strongly contributes to the develo pment of coronary heart disease and is one major factor responsible fo r the familial predisposition to this disease.