Apolipoprotein B-100-containing lipoprotein metabolism in subjects with lipoprotein lipase gene mutations.
Apolipoprotein B-100-containing lipoprotein metabolism in subjects with lipoprotein lipase gene mutations.
复制标题
脂蛋白脂肪酶基因突变受试者中含有载脂蛋白 B-100 的脂蛋白代谢。
DOI：
10.1161/atvbaha.111.238493
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Sprecher,DennisL
中科院分区：
文献类型：
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作者：
Ooi,EstherMM;Russell,BetsyS;Olson,Eric;Sun,SamZ;Diffenderfer,MargaretR;Lichtenstein,AliceH;Keilson,Leonard;Barrett,PHughR;Schaefer,ErnstJ;Sprecher,DennisL
目的探讨脂蛋白脂酶(LPL)基因突变对载脂蛋白B(ApoB)-100代谢的影响。方法与结果研究了3例家族性LPL缺乏症患者，14例LPL基因突变Gly188Glu、Trp64Stop和Ile194Thr杂合子，以及10例对照组。用稳定同位素方法和隔室模型测定摄食状态下极低密度脂蛋白(VLDL)、中密度脂蛋白(IDL)和低密度脂蛋白(LDL)-apoB-100的动力学变化。与对照组相比，家族性LPL缺乏症患者血浆甘油三酯显著升高，VLDL-apoB-100分解代谢率(FCR)、IDL-apoB-100FCR、VLDL-IDL转化率和VLDL-apoB-100产生率显著降低(P<；0.01)。与对照组相比，Gly188Glu组血浆甘油三酯、极低密度脂蛋白和载脂蛋白B-100浓度升高，极低密度脂蛋白和载脂蛋白B-100FCR降低(P<0.05)。Trp64Stop组血浆甘油三酯水平无明显变化，但IDL-apoB-100浓度、载脂蛋白B-100生成率和极低密度脂蛋白-IDL转化率均低于对照组(P<；0.05)。结论高甘油三酯血症是家族性LPL缺乏症的重要特征。这是由于极低密度脂蛋白和低密度脂蛋白-载脂蛋白B-100分解代谢受损以及极低密度脂蛋白向低密度脂蛋白转化所致。LPL基因的单等位基因突变会导致血浆甘油三酯适度或升高。血浆甘油三酯和apoB-100动力学的变化可归因于LPL基因的影响。
ObjectiveWe investigated the impact of lipoprotein lipase (LPL) gene mutations on apolipoprotein B (apoB)-100 metabolism.Methods and ResultsWe studied 3 subjects with familial LPL deficiency; 14 subjects heterozygous for theLPLgene mutations Gly188Glu, Trp64Stop, and Ile194Thr; and 10 control subjects. Very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL)-apoB-100 kinetics were determined in the fed state using stable isotope methods and compartmental modeling. Compared with controls, familial LPL deficiency had markedly elevated plasma triglycerides and lower VLDL-apoB-100 fractional catabolic rate (FCR), IDL-apoB-100 FCR, VLDL-to-IDL conversion, and VLDL-apoB-100 production rate (P<0.01). Compared with controls, Gly188Glu had higher plasma triglyceride and VLDL- and IDL-apoB-100 concentrations and lower VLDL- and IDL-apoB-100 FCR (P<0.05). Plasma triglycerides were not different, but IDL-apoB-100 concentration and production rate and VLDL-to-IDL conversion were lower in Trp64Stop compared with controls (P<0.05). No differences between controls and Ile194Thr were observed.ConclusionOur results confirm that hypertriglyceridemia is a key feature of familial LPL deficiency. This is due to impaired VLDL- and IDL-apoB-100 catabolism and VLDL-to-IDL conversion. Single-allele mutations of theLPLgene result in modest to elevated plasma triglycerides. The changes in plasma triglycerides and apoB-100 kinetics are attributable to the effects of the LPL genotype.