POLYMORPHISM OF APOLIPOPROTEIN-E .3. EFFECT OF A SINGLE POLYMORPHIC GENE LOCUS ON PLASMA LIPID-LEVELS IN MAN

Abstract

The 2 autosomal codominant alleles of the Apo E-N/D [Apolipoprotein E] polymorphism, Apo En and Apo Ed, have a considerable influence on plasma lipid levels and distribution in man. Serum cholesterol levels are highest in phenotype Apo E-N, intermediate in phenotype Apo E-ND and low in phenotype Apo E-D. VLDL[very low density lipoprotein]-cholesterol is highest in phenotype Apo E-D, intermediate in heterozygotes and lowest in phenotype Apo E-N. Serum-triglyceride, VLDL-triglyceride and the ratio of VLDL-cholesterol/serum-triglyceride are also intermediate in phenotype Apo E-ND between the 2 opposite homozygous groups. Of the heterozygous Apo E-ND subjects, 10% exhibited a .beta.-VLDL subfraction compared to 0.8% in phenotype Apo E-N and 100% in Apo E-D. The 3 phenotypic groups exhibit metabolic differences in vivo, and the gene Apo Ed has a mild dyslipoproteinemic effect even in a single dose. The Apo E-N/D polymorphism may be a major influence on the occurrence of arteriosclerotic vascular disease in man.