METAB OF APOLIPOPROTEIN B 100 IN KINDRED W/ FAMILIAL HYPOBETALIPOPROTEINEMIA

家族性低脂蛋白血症（FHBL）存在三种形式(1)

Familial hypobetalipoproteinemia (FHBL) exists in three formsA1) FHBL genetically linked to truncated forms of apolipoprotein B (apoB); b) FHBL linked to the apoB gene but with no apoB truncations; and c) FHBL not linked to the apoB gene. Mean production rate (P) of apoB-100 in FHBL subjects heterozygous for apoB truncations is approximately 30% of normal. In a 49-member D-kindred (FHBL phenotype defined as apoB<40 mg/dl), no apoB truncations were detectable either by immunoblotting of plasma or by sequencing of relevant stretches of the apoB gene. Herein we report on the kinetic parameters of apoB-100-containing lipoproteins in four affected members of the D-kindred, and compare their kinetic values to 14 normal subjects, and 8 previously reported FHBL subjects heterozygous for various truncated forms of apoB. After an 8-h primed intravenous infusion of [13C]-leucine, enrichments of apoB-100 were assessed by gas chromatography-mass spectrometry and kinetic parameters we re calculated by multi-compartmental modeling. The affected members of the D-kindred had similar very low, intermediate, and low density lipoprotein (VLDL, IDL, and LDL) Prs as normal controls, but their fractional catabolic rates (FCR) for VLDL and LDL were approximately 2 and 3 times higher, respectively, than those of normals. By contrast in apoB truncation subjects, apoB-100 Prs were uniformly reduced, while apoB-100 FCRs were similar to normals. Thus, diverse physiologic mechanisms are responsible for the low apoB levels in these two different genetically determined forms of FHBL.