Comparative in vivo metabolism of apolipoproteins E2 and E4 in heterozygous apoE2/4 subjects.
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Apolipoprotein E (apoE) exists in three common forms in humans: the wild-type apoE3 and two common genetic variants, apoE2 and apoE4. Although previous studies have examined the metabolism of the different apoE isoforms in human subjects, they have not involved direct comparison of two different isoforms in subjects heterozygous for the same two isoforms. We conducted this study to directly compare the catabolism of apoE2 and apoE4 in heterozygous E2/4 subjects in vivo. Iodine 131-labeled apoE2 and iodine 125-labeled apoE4 were simultaneously injected into three E4/2 heterozygous subjects. The mean residence time of apoE4 (0.40 +/- 0.01 day) was found to be one-third that of apoE2 (1.20 +/- 0.18 day). ApoE2 was present primarily in high-density lipoprotein, whereas apoE4 was present equally in very low density and high-density lipoprotein. In all lipoprotein subfractions, apoE4 was catabolized at a much faster rate than apoE2. In conclusion, E4 is catabolized three times faster than apoE2 in heterozygous E2/4 subjects, indicating that these two apoE isoproteins have distinct metabolic pathways.