Hyperapobetalipoproteinemia is defined as the combination of a normal
low density lipoprotein (
LDL) cholesterol in the face of an increased
LDL apolipoprotein B (
apoB)
protein. To examine the physical basis for the apparent disproportion between
LDL cholesterol and
apoB characteristic of this syndrome, we used density gradient ultracentrifugation to isolate
LDL fractions from 10 normal subjects, from 20 patients with hyperapobetalipoproteinemia (10 normotriglyceridemic and 10 hypertriglyceridemic), and from 7 patients with
familial hypercholesterolemia. In
familial hypercholesterolemia, more
LDL was in fraction 1--"light"
LDL--and this
LDL was relatively enriched in
cholesterol and poor in
protein. By contrast, it was fraction 2--"heavy"
LDL--that differed in hyperapobetalipoproteinemia, being denser, depleted of
cholesterol (particularly
cholesteryl ester), and relatively enriched in
apoB. These findings were more pronounced in the hypertriglyceridemic patients than in the normotriglyceridemic patients with hyperapobetalipoproteinemia. Thus this study confirms that considerable heterogeneity exists between
LDL subfractions within individuals but, in addition, indicates there are also marked--and apparently characteristic--differences in
LDL composition amongst normal subjects and patients with hyperapobetalipoproteinemia or
familial hypercholesterolemia.