Lack of relationship in humans of the parameters of body cholesterol metabolism with plasma levels of subfractions of HDL or LDL, or with apoE isoform phenotype.

The factors involved in regulating parameters of whole body cholesterol metabolism in humans have been ex- plored in a series of investigations. Several physiological vari- ables have been identified (weight, excess weight, plasma choles- terol, and age) that can predict 53-76% of the variation in production rate (PR) and in the sizes of the rapidly exchanging pool of body cholesterol (M,) and of the minimum estimates of the slowly exchanging pool of body cholesterol (Msmin) and of total body cholesterol (M,,min). Surprisingly, measurements of the plasma levels of HDL cholesterol and of the major HDL apolipoproteins (apoA-I, A-11, and E) did not provide additional information useful in predicting parameters of whole body cho- lesterol metabolism. A study was therefore conducted to investi- gate possible relationships of the plasma levels of subfractions of lipoproteins, determined by analytic ultracentrifugation, and of apoprotein E phenotype, with the parameters of whole body cholesterol metabolism. Ultracentrifugal analysis of plasma lipo- protein subfractions was performed at the Donner Laboratory in 49 subjects; all of these subjects were currently undergoing whole body cholesterol turnover studies or had previously had such studies and were in a similar metabolic state as judged by plasma lipid and lipoprotein values. Apoprotein E phenotyping was carried out in 71 subjects. Differences in model parameters were sought among subjects with various apoprotein E pheno- types. Ultracentrifugal LDL subfractions Ss 0-2 (the region of LPa), Sy 0-7 (smaller LDL), Sy 7-12 (larger LDL), Sy 12- 20 (IDL), and ultracentrifugal HDL subfractions F:.20 0-1.5 (smaller HDLs), FY.20 2-9 (larger HDL3 plus HDL2), and FY,20 5-9 (larger HDL2 or HDL2b) were examined for correlations with each other and with parameters of whole body cholesterol metabolism.lAlthough an interesting negative correlation between the smaller LDL subfraction (Sy 0-7) and the HDL2- enriched subfraction (FY,20 2-9) was confirmed, neither the apo- protein E phenotype nor any of the analytic ultracentrifugal measurements (or their ratios) that were examined provided additional predictive information about parameters of whole body cholesterol metabolism. We conclude that these variables are not important determinants of parameters of whole body cholesterol metabolism in humans, and that other explana- tions must be sought for the remaining variability in these parameters. -Palmer, R. H., A. V. Nichols, R. B. Dell, R. Ramakrishnan, F. T. Lindgren, E. L. Gong, C. B. Blum, and D. S. Goodman. Lack of relationship in humans of the param- eters of body cholesterol metabolism with plasma levels of sub- fractions of HDL or LDL, or with apoE isoform phenotype. J. Lipid Res. 1986. 27: 637-644.