Familial hypertriglyceridemia: an entity with distinguishable features from other causes of hypertriglyceridemia

Abstract

Background Familial hypertriglyceridemia (FHTG) is a partially characterized primary dyslipidemia which is frequently confused with other forms hypertriglyceridemia. The aim of this work is to search for specific features that can help physicians recognize this disease. Methods This study included 84 FHTG cases, 728 subjects with common mild-to-moderate hypertriglyceridemia (CHTG) and 609 normotriglyceridemic controls. All subjects underwent genetic, clinical and biochemical assessments. A set of 53 single nucleotide polymorphisms (SNPs) previously associated with triglycerides levels, as well as 37 rare variants within the five main genes associated with hypertriglyceridemia (i.e. LPL, APOC2, APOA5, LMF1 and GPIHBP1) were analyzed. A panel of endocrine regulatory proteins associated with triglycerides homeostasis were compared between the FHTG and CHTG groups. Results Apolipoprotein B, fibroblast growth factor 21(FGF-21), angiopoietin-like proteins 3 (ANGPTL3) and apolipoprotein A-II concentrations, were independent components of a model to detect FHTG compared with CHTG (AUC 0.948, 95%CI 0.901–0.970, 98.5% sensitivity, 92.2% specificity, P < 0.001). The polygenic set of SNPs, accounted for 1.78% of the variance in triglyceride levels in FHTG and 6.73% in CHTG. Conclusions The clinical and genetic differences observed between FHTG and CHTG supports the notion that FHTG is a unique entity, distinguishable from other causes of hypertriglyceridemia by the higher concentrations of insulin, FGF-21, ANGPTL3, apo A-II and lower levels of apo B. We propose the inclusion of these parameters as useful markers for differentiating FHTG from other causes of hypertriglyceridemia.

Safety and Efficacy of Insulin and Heparin in the Management of Hypertriglyceridemia-Induced Pancreatitis in a Patient without Diabetes: A Case Report

“…Familial hypertriglyceridemia is polygenic and presents with elevated very low-density lipoprotein (VLDL) levels secondary to impaired catabolism of VLDL. In hypertriglyceridemia, VLDL particles contain a higher percentage of TGs, leading to an increased size of VLDL particles and suboptimal hydrolysis by lipoprotein lipase, which ultimately results in a normal amount of VLDL particles with altered compositions [ 23 ].…”

A homozygous variant in the GPIHBP1 gene in a child with severe hypertriglyceridemia and a systematic literature review

“…GPIHBP1 is located on chromosome 8q24.3 and is composed of 4 exons ( Liu et al, 2018 ). GPIHBP1 is expressed mostly in the capillary endothelial cells of the heart, brown adipose tissue and skeletal muscle, involved in energy and lipid metabolism ( Cruz-Bautista et al, 2021 ). GPIHBP1 acts as an important partner of the LPL in plasma triglyceride metabolism ( Supplementary Figure S1 ).…”

Acercamiento a los síndromes de hipertrigliceridemia: la importancia de distinguir entre etiologías primaria y secundaria

“…13 Familial HTG (gype V) highly oligogenic, could be a cause of critical HTG frequently confused with other primary dyslipidemias. 15 A significant number of conditions (Figure 2) that cause mild-tomoderate HTG ought to be excluded. 5…”