Molecular genetic testing and measurement of levels of GPIHBP1 autoantibodies in patients with severe hypertriglyceridemia: The importance of identifying the underlying cause of hypertriglyceridemia.

Autor: Strøm TB; Unit for Cardiac and Cardiovascular Genetics, Oslo University Hospital, Oslo, Norway (Drs Strøm, Bogsrud, Leren). Electronic address: thstro@ous-hf.no., Tveita AA; Section of Clinical Immunology and Infectious Diseases, Department of Rheumatology, Dermatology and Infectious Diseases, Oslo University Hospital, Oslo, Norway (Dr Tveita)., Bogsrud MP; Unit for Cardiac and Cardiovascular Genetics, Oslo University Hospital, Oslo, Norway (Drs Strøm, Bogsrud, Leren)., Leren TP; Unit for Cardiac and Cardiovascular Genetics, Oslo University Hospital, Oslo, Norway (Drs Strøm, Bogsrud, Leren).
Jazyk: angličtina
Zdroj: Journal of clinical lipidology [J Clin Lipidol] 2024 Jan-Feb; Vol. 18 (1), pp. e80-e89. Date of Electronic Publication: 2023 Nov 07.
DOI: 10.1016/j.jacl.2023.11.002
Abstrakt: 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.
Competing Interests: Declaration of Interest Statement The authors declare that there are no competing interests related to this manuscript.
(Copyright © 2023. Published by Elsevier Inc.)
Databáze: MEDLINE
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