Why the study?
The effect of genetic severe hypertriglyceridemia on the lipid profile had primarily been determined using conventional techniques rather than comprehensive profiling methods.
How does the (apo)lipoprotein profile of patients with genetic hypertriglyceridemia differ from normolipidemic controls when assessed by LC-MS and NMR spectroscopy?
How does the (apo)lipoprotein profile of patients with genetic hypertriglyceridemia differ from normolipidemic controls when assessed by LC-MS and NMR spectroscopy?
Patients with genetic hypertriglyceridemia have a lipoprotein profile predominated by large lipoproteins (chylomicrons, VLDL) with an absence of small atherogenic LDL particles, which reduces the accuracy of standard NMR-based models.
Advanced LC-MS/NMR profiling details lipoprotein differences in genetic HTG; leaves open clinical relevance and outcome prediction.
BACKGROUND: 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. OBJECTIVE: To show detailed differences in the (apo)lipoprotein profile of patients with genetic HTG by combining LC-MS and NMR techniques. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Straat et al. (2022) studied this question.
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