The lipoprotein analysis of 4 subjects with Type III hyper lipoproteinemia associated with Apo E3 deficiency was performed by high performance liquid chromatography (HPLC) in addition to ultracentrifugation and PAG-disc electrophoresis and the results were compared with those of 3 subjects with familial hypercholesterolemia showing the phenotype of Type III (FH-Type III) classified by β-migrating VLDL and increase of IDL but without Apo E3 deficiency. VLDL subfraction contained increased concentration of cholesterol and triglyceride and were relatively rich in cholesterol in both classical Type III and FH-Type III. LDL subfraction in classical Type III was very low and the ratio of cholesterol to triglyceride was low even before treatment when total cholesterol was high, while FH-Type III had high level of LDL-cholesterol. HPLC for lipoprotein revealed no lipoprotein eluted at the regular LDL position and elution position of major component shifted to the position of larger particle size than LDL. In FH-Type III major fraction was eluted at the exact position of normal LDL, although PAG-disc electrophoresis showed broad-β pattern similar to classical Type III.
Clofibrate treatment decreased cholesterol and triglyceride level to normal ranges although no change was occured in electrophoretic pattern and elution pattern of HPLC in classical Type III. However, in FH-Type III broad-β pattern disappeared and was onverted to typical Type IIa by clofibrate treatment. From the data above, we conclude that the mechanism of the appearance of Type III phenotype was clearly different between classical Type III with Apo E3 and the others and it is possible even without Apo E analysis to diagnose classical Type III (E2/2) by lipoprotein analysis using HPLC and by the mode of responses to clofibrate treatment.
