METAB OF APOLIPOPROTEIN B 100 IN KINDRED W/ FAMILIAL HYPOBETALIPOPROTEINEMIA

家族性低脂蛋白血症(FHBL)以三种形式存在 FHBL与截短形式的载脂蛋白B(ApoB)基因连锁； B)与apoB基因连锁但没有apoB截断的FHBL；以及c) FHBL不与apoB基因连锁。平均生产率(P) FHBL患者apoB-100基因缺失杂合子为 大约是正常的30%。在一个49人的D-家系(FHBL表型 定义为apoB；40 mg/dl)，也没有检测到apoB截断 通过血浆免疫印迹或通过对相关片段进行测序 载脂蛋白B基因。在这里，我们报告了动力学参数 四个受影响成员中含ApoB-100的脂蛋白 D-家系，并与14名正常受试者比较他们的动力学值，以及 8例先前报道的FHBL受试者为各种截短杂合子 载脂蛋白B的形式。在8小时内预先静脉滴注 [13C]-亮氨酸，用GAS法测定apoB-100的丰度 色质联用和动力学参数 通过多室模型计算。受影响的成员 D系具有类似的极低、中等和低密度 脂蛋白(极低密度脂蛋白、低密度脂蛋白和低密度脂蛋白)作为正常对照，但其 极低密度脂蛋白和低密度脂蛋白的部分分解代谢率(FCR)约为2 分别是正常人的3倍。相比之下， 在apoB截短受试者中，apoB-100 PR均匀减少， 而apoB-100FCR与正常人相似。因此，多样化 低载脂蛋白B水平的生理机制 这两种不同的基因决定的FHBL形式。

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.