Distribution of apolipoprotein E between apo B- and non apo B-containing lipoproteins according to apo E phenotype

Apolipoprotein E (apo E) is a component of all the classes of lipoproteins and can be distributed among apo B- (LpB) and non apo B-containing lipoproteins (Lp-non-B). Using a new electroimmunoassay kit, plasma apo E, apo E in Lp-non-B (apo E–Lp-non-B) and apo E in LpB (apo E–LpB) levels were measured in healthy control subjects (n=481) from 3 centers participating in the ECTIM study (Etude Cas-Témoins sur lʹInfarctus du Myocarde), a population-based study on myocardial infarction. The distribution of apo E among lipoproteins was analyzed according to the apo E phenotype after adjustment for center, body mass index, tobacco use, alcohol consumption and triglycerides. Apo E was higher (average excess:+0.32; P<0.0001) and lower (average excess:−0.12; P<0.0001) in subjects carrying the allele 2 and the allele 4 respectively, than in apo E3/3 subjects. These differences are the consequence of variations in apo E–Lp-non-B which clearly differed between the groups classified according to their apo E phenotype (P<0.0001). The average excess of apo E Lp–non-B compared to apo E3/3 subjects was +0.43 (P<0.0001) and −0.22 (P<0.0001) for the 2 and 4 alleles respectively. Apo E–LpB was lower in subjects carrying the 2 allele (P<0.02) while the presence of the 4 allele did not modify this parameter. The proportion of apo E within HDL was clearly higher and lower in subjects carrying apo E2 and apo E4 respectively than in apo E3/3 subjects. Although triglyceride levels were dependent on the apo E phenotype, the adjustment of the proportion of apo E in HDL for triglycerides hardly modified the results. For the first time, these results, using direct measurements on a large number of subjects, confirm the greater preference of apo E4 over apo E2 for LpB and vice versa for Lp-non-B. They also show a greater affinity of apo E2 for HDL compared to apo E3. This high affinity of apo E2 for HDL could be due to the formation of the apo E–A-II complex. These results indicate that apo E phenotype modulates the distribution of apo E among lipoproteins and suggest differences in lipoprotein metabolism between apo E2, apo E3 and apo E4.