Familial apolipoprotein CII deficiency: plasma lipoproteins and apolipoproteins in heterozygous and homozygous subjects and the effects of plasma infusion

Abstract. Plasma lipoproteins and apolipoproteins have been studied in a kindred with familial apolipoprotein CII (apo CII) deficiency. As in two other recently documented pedigrees, apo CII deficiency appeared to be transmitted as an autosomal recessive trait. The homozygous state was characterized by gross fasting hypertriglyceridaemia, complete absence of apo CII from plasma and failure of plasma to activate lipoprotein lipase. Post-heparin plasma hepatic triglyceride lipase activity was normal. Hypertriglyceridaemia reflected chylomicronaemia and elevated Sf 100–400 and Sf 20–100 lipoprotein concentrations; lipoproteins of Sf 12–20 (LDL₁), Sf 0–12 (LDL₂), F_1.23.5–9 (HDL₂) and F_1.20–3.5 (HDL₃) were greatly reduced in concentration. Low density lipoproteins (1.006–1.063 g/ml), isolated by preparative ultracentrifugation, and high density lipoproteins, isolated by heparin/Mn⁺⁺, were triglyceride-enriched. Electroimmunoassays revealed additionally low plasma concentrations of apolipoproteins AI, AII and B and very high concentrations of apolipoproteins CIII and E in the homozygote. The parents of the proband (heterozygotes) were normotriglyceridaemic, and had normal lipoprotein lipid concentrations and normal apolipoprotein AI, AII, B, CIII and E concentrations, in spite of having low apo CII concentrations. Activation of lipoprotein lipase in the homozygote by intravenous infusion of 200 ml fresh-frozen plasma rapidly reduced the plasma concentrations of chylomicrons and very low density lipoproteins (VLDL). Within VLDL, the decrease in concentration occurred sequentially in the Sf 100–400 and Sf 20–100 subclasses. These changes were associated during a 4-day study period with reciprocal increases in LDL₁, LDL₂, HDL₂ and HDL₃. The plasma concentrations of apo AI and apo B also increased, associated with a less marked fall in that of apo CIII; the apo AII and apo E concentrations were unchanged. These observations support other evidence that apo CII is a cofactor for the catabolism of chylomicrons and both major subfractions of VLDL by lipoprotein lipase in man, and that human LDL₁ and LDL₂ are derived, at least in part, from triglyceride-rich lipoprotein catabolism. They also suggest that both major subfractions of HDL acquire additional components during triglyceride-rich lipoprotein catabolism. In normal subjects the plasma apo CII concentration appears to be greatly in excess of that required for adequate activation of lipoprotein lipase.