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 comparison of offspring having a paternal history of premature myocardial infarction with age- and sex-matched control subjects. Case (n = 635) and control (n = 1259) subjects aged 18 through 26 years were recruited from 14 universities of 11 European countries. The allele distributions of apolipoprotein (apo) E polymorphism differed between populations, with 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 gradient of coronary heart disease mortality rates. The association of apoE polymorphism with plasma total cholesterol, low-density lipoprotein cholesterol, apoB, and apoE levels was consistent with the now well-identified effects of epsilon 2 and epsilon 4 alleles on these traits. Both epsilon 2 and epsilon 4 alleles equally increased the level of triglycerides, and epsilon 2 had a lowering effect on lipoprotein(a) concentration. There were also weak effects of epsilon 2 and epsilon 4 on high-density lipoprotein cholesterol, apoA-I, and apoA-I-containing lipoprotein levels that paralleled those on apoE levels. The main finding of 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 region, 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 the case/control difference of apoB level. These results provide a body of evidence that apoE polymorphism strongly contributes to the development of coronary heart disease and is one major factor responsible for the familial predisposition to this disease.