Plasma
lipoprotein concentration, composition, and size were evaluated in two common familial forms of
hypertriglyceridemia and compared with those in normal subjects. The
very low density lipoproteins (VLDL) were
triglyceride-enriched in
familial hypertriglyceridemia (
triglyceride/
apoprotein B ratio: 25.7 +/- 8.9) as compared to normal (9.6 +/- 12.2, P < 0.001) or
familial combined hyperlipidemia (9.7 +/- 3.3, P < 0.001). The diameter of VLDL was larger in
familial hypertriglyceridemia (3.27 +/- 0.28 pm) than in
familial combined hyperlipidemia (2.87 +/- 0.16 pm, P < 0.02). Although in
familial hypertriglyceridemia VLDL tended to be larger, and in
familial combined hyperlipidemia VLDL tended to be smaller than normal (3.08 +/- 0.48 pm), neither of these differences were significant. While VLDL was normally distributed in the control population, the size was skewed to larger particles in
familial hypertriglyceridemia with fewer small particles (P < 0.05) and skewed to smaller particles in
familial combined hyperlipidemia with fewer large particles (P < 0.05). VLDL was reciprocally related to
low density lipoproteins (
LDL) in familial combined hyperlipidemia (r = -0.80 to -0.87) suggesting that the concentrations of these individual
lipoprotein groups were somehow interrelated. There was no significant relationship between these two
lipoprotein classes in
familial hypertriglyceridemia or in normals. In
familial combined hyperlipidemia, the
apoprotein A-I/A-II ratio was below normal (P < 0.01) suggestive of low
HDL(2) levels. This change in
apoprotein composition was independent of VLDL or
LDL concentration. In
familial hypertriglyceridemia,
high density lipoprotein (
HDL) cholesterol was reduced (33% below mean normal) and
HDL triglyceride was increased (by 46%), while the concentration of
apoA-I and
apoA-II was normal.
VLDL triglyceride was inversely related to
HDL cholesterol in
familial hypertriglyceridemia (r = -0.74, P < 0.005), but not in
familial combined hyperlipidemia. The large,
triglyceride-enriched VLDL observed in
familial hypertriglyceridemia is compatible with the reported increase in
VLDL triglyceride synthesis seen in this disorder. The increase in VLDL
apoprotein B synthesis previously reported in
familial combined hyperlipidemia was associated with VLDL of normal composition. The changes in
HDL cholesterol in these two disorders might reflect exchange of
triglyceride between VLDL and HDL or could be related to transfer of surface components during the catabolism of VLDL. The reciprocal relationship between various components of VLDL and
LDL seen in
familial combined hyperlipidemia, but not in
familial hypertriglyceridemia or in normal subjects, might provide some insight into the pathological abnormalities in these disorders. The differences between these two common familial forms of
hypertriglyceridemia provide further support that they are distinct entities.-Brunzell, J. D., J. J. Albers, A. Chait, S. M. Grundy, E. Groszek, and G. B. McDonald. Plasma
lipoproteins in
familial combined hyperlipidemia and monogenic
familial hypertriglyceridemia.