APOLIPOPROTEIN-E AND ATHEROSCLEROSIS IN ALASKA NATIVES

Arterial, liver, and serum specimens were collected from 130 Alaska Na tives who underwent forensic necropsy (mean age, 36.9 years; age range , 9-85 years; 38 females and 92 males). Based upon the observed freque ncies of the six common apo E genotypes, the estimates of the relative frequencies of the corresponding alleles in the population are 0.020 +/- 0.009 for E2, 0.787 +/- 0.026 for E3 and 0.193 +/- 0.025 for E4. A nalysis showed significant differences, by apo E genotype, in the exte nt of total surface lesion involvement in both the right and left coro nary arteries. In all but the abdominal aorta, the pattern of lesion i nvolvement by genotype is consistent with a decrease in lesions for ge notypes with the E2 allele and an increase in lesions for the genotype s with the E4 allele, relative to the E3 homozygotes. After adjustment for low + very low density lipoprotein cholesterol (LDL + VLDL-C), th e differences fell below statistically significant levels. Analysis by genotype of total serum cholesterol, high density lipoprotein cholest erol (HDL-C) and LDL + VLDL-C showed no statistically significant diff erences in analyte levels among genotypes. However, evidence is seen o f a pattern in which total cholesterol and VLDL + LDL-C is less in gen otypes with the E2 allele and greater in those with the E4 allele. We conclude that there does appear to be an effect by apo E genotype upon extent of atherosclerosis in the coronary arteries of Alaska Natives and this effect is likely due to the previously reported effect of apo E polymorphisms on serum cholesterol, particularly LDL + VLDL-C.