Key result
Molecular genetic testing and autoantibody measurement in patients with severe hypertriglyceridemia identified a monogenic cause in 0.9% and GPIHBP1 autoantibody syndrome in 0.8%.
Why the study?
Severe hypertriglyceridemia can stem from pathogenic variants in triglyceride metabolism genes or GPIHBP1 autoantibodies, but their contribution required identification in clinical cohorts.
Observational (n=459)
Monogenic mutations and GPIHBP1 autoantibodies are rare but important underlying causes of severe hypertriglyceridemia, highlighting the potential utility of specific diagnostic testing to guide appropriate therapy.
Low yield of monogenic (0.9%) or GPIHBP1 autoantibody causes in severe hypertriglyceridemia; leaves optimal testing and tailored therapy open for prospective study.
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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Strøm et al. (2023) conducted an observational in Severe hypertriglyceridemia (n=459). Molecular genetic testing and GPIHBP1 autoantibody measurement was evaluated on Identification of a monogenic cause of hypertriglyceridemia. Molecular genetic testing and autoantibody measurement in patients with severe hypertriglyceridemia identified a monogenic cause in 0.9% and GPIHBP1 autoantibody syndrome in 0.8%.
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