APOLIPOPROTEIN (APO)-E GENOTYPE AND APOE CONCENTRATION DETERMINE BINDING OF NORMAL VERY-LOW-DENSITY LIPOPROTEINS TO HEPG2 CELL-SURFACE RECEPTORS

The clinical relevance of apoE concentration in lipoprotein fractions should be evaluated. We investigated the impact of the common apolipop rotein (apo) E polymorphism in conjunction with very low density Lipop rotein (VLDL) apoE, concentration on the receptor binding properties o f VLDL preparations from 17 normolipidemic subjects to the HepG2 cell surface receptors. All six apoE genotypes were studied When apoE genot ype alone was considered, two subgroups could be distinguished: VLDL w ithout apoE isoform E2 (VLDL-3/3, VLDL-3/4, and VLDL-4/4) showed signi ficantly higher affinity than VLDL with apoE2 (VLDL-4/2, VLDL-3/2, and VLDL-2/2). Once we adjusted for VLDL apoE content, we observed that V LDL affinity to HepG2 cell surface receptors decreased, according to a poE genotype, in the following order: VLDL-4/4 (100%) > VLDL-3/4 (93%) > VLDL-3/3 (82%)> VLDL-4/2 (53%) > VLDL-3/2 (36%) > VLDL-2/2 (30%). M oreover, we found that VLDL apoE concentration could modify isoform-sp ecific binding. An analysis in 47 subjects showed that the concentrati on of total VLDL protein and the VLDL apoE concentration varied consid erably. The variation of VLDL apoE was independent of apoE genotype an d corresponding serum apoE levels. We conclude that, in addition to ap oE genotype, apoE content of VLDL is an important determinant of the r eceptor binding properties of VLDL.