Apolipoprotein E polymorphism and the distribution profile of very low density lipoproteins; an influence of the E4 allele on large (Sf>60) particles Original Research Article

Very low density lipoprotein (VLDL) distribution and composition have been examined as a function of apo E genotype (E2/2+E2/3 vs. E3/3 vs. E3/4+E4/4) in healthy, normolipaemic subjects. Apo E genotype had a marked impact on plasma concentrations of apo E rich VLDL, but no influence on concentrations of apo E free particles. Thus, there was a trend to lower concentrations of apo E rich total VLDL in apo E4 carriers (mg/dl; E2, 49.1±35.2; E3, 52.5±30.9; E4 35.2±22.3; ANOVA P=0.16; when comparing E4 with E2+E3, P=0.06). Consequently, there were highly significant differences between apo E-defined subgroups in terms of the percentage distribution of bound and non-bound fractions (% total VLDL non-bound to apo E: E2, 44.0±12.7%; E3, 39.7±8.7%; E4 51.0±12.2%; ANOVA P=0.007). Subfractionation of VLDL into density subclasses revealed that genotype differences were restricted to large VLDL (Sf>60). Significantly lower concentrations of apo E-rich particles were observed in E4 carriers for VLDL-1 Sf 400–100 (ANOVA P=0.004) and VLDL-2 (P=0.009) but not for small VLDL-3 Sf 60–20 (P=0.34). No differences in plasma concentrations of apo E free VLDL were observed between genotype subclasses across the density spectrum. Compositional differences between the apo E defined VLDL were also evident for the core lipids. Apo E containing VLDL was enriched in esterified cholesterol and depleted in triglycerides compared to apo E poor VLDL: the difference became more marked with increasing density of the particles. Lipoprotein composition was not modulated to any great extent by apo E genotype. In patients with familial hypercholesterolaemia, relative concentrations of apo E rich, large VLDL were significantly higher than in controls. Treatment lowered concentrations of both apo E rich and apo E free VLDL but led to a greater relative enrichment of large VLDL in apo E containing particles. Apo E polymorphism appears to influence plasma concentrations of VLDL particles. The data are consistent with more pronounced receptor-mediated elimination of apo E4 containing VLDL. This may be a contributory factor to the down regulation of receptor activity which is suggested to be of major importance in provoking higher cholesterol levels associated with the apo E4 isoform.