METAB OF APOLIPOPROTEIN B 100 IN KINDRED W/ FAMILIAL HYPOBETALIPOPROTEINEMIA

家族性低β脂蛋白血症亲属中载脂蛋白 B 100 的代谢分析

• 批准号: 6118549
• 负责人: MICKEY A LATOUR
• 金额: $ 0.48万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6118549
• 关键词: biomedical resource; cardiovascular system; female; genetics; human subject; lipids; male; proteins; spectrometry

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.

家族性低β脂蛋白血症（FHBL）有三种形式： FHBL与截短形式的载脂蛋白B（apo B）遗传连锁; B）与apo B基因连接但没有apo B截短的FHBL;和 FHBL与apoB基因无关。 平均生产率（P） apoB截短杂合子的FHBL受试者的apoB-100 正常的30%左右。 在一个由49名成员组成的D-亲属（FHBL表型）中 定义为apoB<40 mg/dl），也未检测到apoB截短 通过血浆的免疫印迹或通过对相关片段的测序， apoB基因 在这里，我们报告的动力学参数， 在四个受影响的成员中含有载脂蛋白B-100的脂蛋白 与14名正常人进行比较， 8例既往报告的FHBL受试者为各种截短型杂合子 apoB的形式。 在预充静脉输注8小时后， [13 C]-亮氨酸，apoB-100的富集通过气相色谱法进行评估。 色谱-质谱和动力学参数，我们 通过多房室模型计算。 受影响的成员 D-亲属有相似的极低、中等和低密度 脂蛋白（VLDL，IDL和LDL）Prs作为正常对照，但其 VLDL和LDL的分解率（FCR）约为2 和3倍。 相比之下 在apoB截短受试者中，apoB-100 Prs均匀降低， 而apoB-100 FCR与正常人相似。 因此， 生理机制是造成低载脂蛋白B水平， 这两种不同的基因决定的FHBL形式。