Apolipoprotein E polymorphisms affect atherosclerosis in young males. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group

Abstract

Investigators in eight communities collected aortas, right coronary arteries, blood and liver samples, and associated information from 720 young males, aged 15-34 years, who died of external causes. Genotypes for apolipoprotein (apo) E isoforms (E2, E3, and E4) were determined from hepatic DNA by restriction isotyping (restriction enzyme isoform genotyping) of amplified apo E sequences. Pathologists graded the arteries for atherosclerotic lesions, and a central laboratory measured lipoprotein cholesterol concentrations. Allele frequencies were different between blacks and whites (p less than 0.0001). E2 and E4 frequencies were higher and E3 frequency was lower in blacks than in whites. Among the common genotypes in both whites and blacks, E2E3 heterozygotes had the lowest levels of total serum cholesterol and low density lipoproteins, E3E4 had the highest levels, and E3E3 had intermediate levels. Apo E genotypes differed in mean percent surface area involvement with lesions in the thoracic aorta and the abdominal aorta of both whites and blacks (p less than or equal to 0.0002). Among the common genotypes, E2E3 heterozygotes had the least involvement of both thoracic and abdominal aortas with lesions, E3E4 had the greatest involvement (with the exception of the thoracic aorta in whites), and E3E3 had intermediate involvement. Apo E genotype accounted for 5.7% in whites and 5.9% in blacks of the observed variation in lesions for the thoracic aorta, and for 5.9% in whites and 7.0% in blacks for the abdominal aorta. Adjusting for cholesterol levels did not change apo E genotypic effects appreciably, an observation suggesting that genotypic effects on arterial lesions may not be mediated entirely by changes in serum cholesterol concentrations.