Article: Molecular genetic testing and measurement of levels of GPIHBP1 autoantibodies in patients with severe hypertriglyceridemia: The importance of identifying the underlying cause of hypertriglyceridemia.
Journal of clinical lipidology
2023 Volume 18, Issue 1, Page(s) e80–e89
Abstract: Background: Severe hypertriglyceridemia can be caused by pathogenic variants in genes encoding proteins involved in the metabolism of triglyceride-rich lipoproteins. A key protein in this respect is lipoprotein lipase (LPL) which hydrolyzes ... ...
| Abstract | Background: Severe hypertriglyceridemia can be caused by pathogenic variants in genes encoding proteins involved in the metabolism of triglyceride-rich lipoproteins. A key protein in this respect is lipoprotein lipase (LPL) which hydrolyzes triglycerides in these lipoproteins. Another important protein is glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) which transports LPL to the luminal side of the endothelial cells. Objective: Our objective was to identify a genetic cause of hypertriglyceridemia in 459 consecutive unrelated subjects with levels of serum triglycerides ≥20 mmol/l. These patients had been referred for molecular genetic testing from 1998 to 2021. In addition, we wanted to study whether GPIHBP1 autoantibodies also were a cause of hypertriglyceridemia. Methods: Molecular genetic analyses of the genes encoding LPL, GPIHBP1, apolipoprotein C2, lipase maturation factor 1 and apolipoprotein A5 as well as apolipoprotein E genotyping, were performed in all 459 patients. Serum was obtained from 132 of the patients for measurement of GPIHBP1 autoantibodies approximately nine years after molecular genetic testing was performed. Results: A monogenic cause was found in four of the 459 (0.9%) patients, and nine (2.0%) patients had dyslipoproteinemia due to homozygosity for apolipoprotein E2. One of the 132 (0.8%) patients had GPIHBP1 autoantibody syndrome. Conclusion: Only 0.9% of the patients had monogenic hypertriglyceridemia, and only 0.8% had GPIHBP1 autoantibody syndrome. The latter figure is most likely an underestimate because serum samples were obtained approximately nine years after hypertriglyceridemia was first identified. There is a need to implement measurement of GPIHBP1 autoantibodies in clinical medicine to secure that proper therapeutic actions are taken. |
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| MeSH term(s) | Humans ; Autoantibodies ; Endothelial Cells ; Receptors, Lipoprotein ; Lipoprotein Lipase/genetics ; Lipoprotein Lipase/metabolism ; Lipoproteins ; Hypertriglyceridemia/genetics ; Triglycerides/metabolism ; Molecular Biology ; Apolipoproteins |
| Chemical Substances | Autoantibodies ; Receptors, Lipoprotein ; Lipoprotein Lipase (EC 3.1.1.34) ; Lipoproteins ; Triglycerides ; Apolipoproteins ; GPIHBP1 protein, human |
| Language | English |
| Publishing date | 2023-11-07 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 2365061-8 |
| ISSN | 1876-4789 ; 1933-2874 |
| ISSN (online) | 1876-4789 |
| ISSN | 1933-2874 |
| DOI | 10.1016/j.jacl.2023.11.002 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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