LIPOPROTEINS IN FAMILIAL DYSBETALIPOPROTEINEMIA - VARIATION OF SERUM-CHOLESTEROL LEVEL ASSOCIATED WITH VLDL CONCENTRATION

Patients with familial dysbetalipoproteinemia (FD) associated with the apo E2/2 phenotype exhibit a marked interindividual variability in serum cholesterol and triglyceride concentrations. It has been proposed that this variability is due to a combination of the apo E2/2 phenotype and additional genetic factors implicated in diseases like familial hypercholesterolemia, familial combined hyperlipoproteinemia, and familial hypertriglyceridemia. To further explore the nature of this variability, the lipoprotein profiles of 17 patients with FD associated with the apo E2/2 phenotype were analyzed by a density-gradient ultracentrifugation technique and by 2-16% polyacrylamide gel electrophoresis. It was found that all patients with FD were characterized by 1) markedly increased cholesterol concentrations of large very low density lipoprotein (VLDL) (VLDL1) (2.98+/-3.08 versus 0.08+/-0.03 mmol/L), small VLDL (VLDL2) (4.68+/-1.93 versus 0.27+/-0.13 mmol/L), and intermediate density lipoprotein (IDL) (2.25+/-0.72 versus 0.39+/-0.16 mmol/L); 2) decreased low density lipoprotein (LDL) cholesterol level (1.84+/-0.54 versus 3.36+/-0.53 mmol/L); and 3) altered composition (enrichment by cholesteryl ester) of VLDL1 and VLDL2 compared with normolipidemic control subjects. The cholesterol levels of IDL and LDL showed minor interindividual variabilities and were not correlated with serum cholesterol and triglyceride levels. The compositions of VLDL1 and VLDL2 were independent of the concentrations of lipids in serum. However, the cholesterol concentrations of VLDL1 and VLDL2 showed considerable interindividual variabilities and were positively correlated with the serum cholesterol concentration (r=0.84 and r=0.95, respectively, both p<0.001). It is concluded that the marked interindividual variability in the serum cholesterol and triglyceride concentrations in patients with FD is mainly due to variations in the concentrations of VLDL1 and VLDL2. This suggests that a combination of the apo E2/2 phenotype and genetic abnormalities in the metabolism of triglyceride-rich lipoproteins may be required for the expression of FD.