Straat Maaike E, Martinez-Tellez Borja, Nahon Kimberly J, Janssen Laura G M, Verhoeven Aswin, van der Zee Leonie, Mulder Monique T, Kooijman Sander, Boon Mariëtte R, van Lennep Jeanine E Roeters, Cobbaert Christa M, Giera Martin, Rensen Patrick C N
Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
J Clin Lipidol. 2022 Jul-Aug;16(4):472-482. doi: 10.1016/j.jacl.2022.04.004. Epub 2022 Apr 30.
Mutations in genes encoding lipoprotein lipase (LPL) or its regulators can cause severe hypertriglyceridemia (HTG). Thus far, the effect of genetic HTG on the lipid profile has been mainly determined via conventional techniques.
To show detailed differences in the (apo)lipoprotein profile of patients with genetic HTG by combining LC-MS and NMR techniques.
Fasted serum from 7 patients with genetic HTG and 10 normolipidemic controls was used to measure the concentration of a spectrum of apolipoproteins by LC-MS, and to estimate the concentration and size of lipoprotein subclasses and class-specific lipid composition using NMR spectroscopy.
Patients with genetic HTG compared to normolipidemic controls had higher levels of apoB48 (fold change [FC] 11.3, P<0.001), apoC-I (FC 1.5, P<0.001), apoC-II (FC 4.3, P=0.007), apoC-III (FC 3.4, P<0.001), and apoE (FC 4.3, P<0.001), without altered apoB100. In addition, patients with genetic HTG had higher concentrations of TG-rich lipoproteins (i.e., chylomicrons and very low-density lipoproteins [VLDL]; FC 3.0, P<0.001), but lower LDL (FC 0.4, P=0.001), of which medium and small-sized LDL particles appeared even absent. While the correlation coefficient between NMR and enzymatic analysis in normolipidemic controls was high, it was considerably reduced in patients with genetic HTG.
The lipoprotein profile of patients with genetic HTG is predominated with large lipoproteins (i.e., chylomicrons, VLDL), explaining high levels of apoC-I, apoC-II, apoC-III and apoE, whereas small atherogenic LDL particles are absent. The presence of chylomicrons in patients with HTG weakens the accuracy of the NMR-based model as it was designed for normolipidemic fasted individuals.
编码脂蛋白脂肪酶（LPL）或其调节因子的基因突变可导致严重的高甘油三酯血症（HTG）。到目前为止，遗传性HTG对血脂谱的影响主要通过传统技术来确定。
通过结合液相色谱-质谱联用（LC-MS）和核磁共振（NMR）技术，展示遗传性HTG患者（载）脂蛋白谱的详细差异。
采用7例遗传性HTG患者和10例血脂正常对照者的空腹血清，通过LC-MS测量一系列载脂蛋白的浓度，并使用NMR光谱估计脂蛋白亚类的浓度和大小以及类特异性脂质组成。
与血脂正常对照者相比，遗传性HTG患者的载脂蛋白B48水平更高（倍数变化[FC] 11.3，P<0.001）、载脂蛋白C-I（FC 1.5，P<0.001）、载脂蛋白C-II（FC 4.3，P=0.007）、载脂蛋白C-III（FC 3.4，P<0.001）和载脂蛋白E（FC 4.3，P<0.001），而载脂蛋白B100未改变。此外，遗传性HTG患者富含甘油三酯的脂蛋白（即乳糜微粒和极低密度脂蛋白[VLDL]；FC 3.0，P<0.001）浓度更高，但低密度脂蛋白（LDL）更低（FC 0.4，P=0.001），其中中型和小型LDL颗粒甚至缺失。虽然血脂正常对照者中NMR与酶分析之间的相关系数较高，但在遗传性HTG患者中显著降低。
遗传性HTG患者的脂蛋白谱以大脂蛋白（即乳糜微粒、VLDL）为主，这解释了载脂蛋白C-I、载脂蛋白C-II、载脂蛋白C-III和载脂蛋白E的高水平，而致动脉粥样硬化的小LDL颗粒不存在。HTG患者中乳糜微粒的存在削弱了基于NMR的模型的准确性，因为该模型是为血脂正常的空腹个体设计的。
