Effects of ApoE genotype on ApoB-48 and ApoB-100 kinetics with stable isotopes in humans.
Effects of ApoE genotype on ApoB-48 and ApoB-100 kinetics with stable isotopes in humans.
复制标题
ApoE 基因型对人类稳定同位素 ApoB-48 和 ApoB-100 动力学的影响。
DOI：
10.1161/01.atv.20.7.1807
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Schaefer,EJ
中科院分区：
文献类型：
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作者：
Welty,FK;Lichtenstein,AH;Barrett,PH;Jenner,JL;Dolnikowski,GG;Schaefer,EJ
- 具有载脂蛋白（apo）E4等位基因的受试者已经显示出比具有其他等位基因的受试者具有更高的低密度脂蛋白（LDL）胆固醇和apoB水平。为了阐明导致这一发现的代谢机制，我们通过使用预充的恒定输注[5，5，在18名血脂正常的受试者中，12名具有apoE 3/E3基因型，6名具有apoE 3/E4基因型，在进食平均美国饮食期间，在进食状态下（每小时进食）5- 2 H3]亮氨酸。通过超离心分离脂蛋白和载脂蛋白，通过十二烷基硫酸钠凝胶;同位素富集通过气相色谱-质谱法进行评估。用saamII软件对数据进行多房室模型计算动力学参数。与apoE 3/E3受试者相比，apoE 3/E4受试者的总apoB水平显著更高，分别为100.1±17.8和135.4±34.0 mg/dL（P=0.009），LDL apoB-100水平显著更高，分别为88.1±19.2和127.5±32.7 mg/dL（P=0.005）。apoE 3/E4受试者的TRL apoB-48样本量比apoE 3/E3受试者低17.4%，因为apoE 3/E3受试者的生产率低33.3%（P=0.28）。TRL apoB-48部分分解代谢率无显著差异（5.1±2.2 vs 5.0±2.1合并液/天）。与apoE 3/E3受试者相比，apoE 3/E4受试者的VLDL apoB-100合并量低36%，这完全是因为apoE 3/E3受试者的生产率低30%（P=0.04）。与apoE 3/E3受试者相比，apoE 3/E4受试者的LDL apoB-100池大小高57.8%（P=0.003），这是由于LDL apoB-100的部分分解率低35.5%（P=0.003），产生率无显著差异。此外，apoE 3/E4受试者中77%的VLDL apoB-100转化为LDL apoB-100，而apoE 3/E3受试者中58%转化为LDL apoB-100（P=0.05）。总之，1个E4等位基因的存在与LDL apoB-100水平较高相关，因为LDL apoB-100的催化分数较低，VLDL apoB-100转化为LDL apoB-100增加了33%。
—Subjects with the apolipoprotein (apo) E4 allele have been shown to have higher low density lipoprotein (LDL) cholesterol and apoB levels than do subjects with the other alleles. To elucidate the metabolic mechanisms responsible for this finding, we examined the kinetics of apoB-48 within triglyceride-rich lipoproteins (TRLs) and of apoB-100 within very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and LDL by using a primed constant infusion of [5,5,5-2H3]leucine in the fed state (hourly feeding) during consumption of an average American diet in 18 normolipidemic subjects, 12 of whom had the apoE3/E3 genotype and 6, the apoE3/E4 genotype. Lipoproteins were isolated by ultracentrifugation and apolipoproteins, by sodium dodecyl sulfate gels; isotope enrichment was assessed by gas chromatography–mass spectrometry. Kinetic parameters were calculated by multicompartmental modeling of the data withsaamII software. Compared with the apoE3/E3 subjects, the apoE3/E4 subjects had significantly higher levels of total apoB, 100.1±17.8 versus 135.4±34.0 mg/dL (P=0.009), and significantly higher levels of LDL apoB-100, 88.1±19.2 versus 127.5±32.7 mg/dL (P=0.005), respectively. The pool size of TRL apoB-48 was 17.4% lower for apoE3/E4 subjects compared with apoE3/E3 subjects due to a 33.3% lower production rate (P=0.28). There was no significant difference in the TRL apoB-48 fractional catabolic rate (5.1±2.2 versus 5.0±2.1 pools per day). The pool size for VLDL apoB-100 was 36% lower for apoE3/E4 subjects compared with apoE3/E3 subjects due entirely to a 30% lower production rate (P=0.04). The LDL apoB-100 pool size was 57.8% higher (P=0.003) for apoE3/E4 subjects compared with apoE3/E3 subjects due to a 35.5% lower fractional catabolic rate of LDL apoB-100 (P=0.003), with no significant difference in production rate. In addition, 77% of VLDL apoB-100 was converted to LDL apoB-100 in apoE3/E4 subjects compared with 58% in apoE3/E3 subjects (P=0.05). In conclusion, the presence of 1 E4 allele was associated with higher LDL apoB-100 levels owing to lower fractional catabolism of LDL apoB-100 and a 33% increase in the conversion of VLDL apoB-100 to LDL apoB-100.