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

Lipids Health Dis. 2021 Feb 15;20(1):14. doi: 10.1186/s12944-021-01436-6.

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.

Keywords: ANGPTL3; Apolipoprotein B; Chylomicronemia; FGF-21; Familial hypertriglyceridemia; Mexicans; Primary dyslipidemias.

MeSH terms

  • Adult
  • Angiopoietin-Like Protein 3
  • Angiopoietin-like Proteins / genetics*
  • Apolipoprotein A-II / genetics*
  • Apolipoprotein A-V / genetics
  • Apolipoprotein C-II / genetics
  • Apolipoproteins B / genetics
  • Diagnosis, Differential
  • Female
  • Fibroblast Growth Factors / genetics*
  • Humans
  • Hyperlipoproteinemia Type IV / diagnosis*
  • Hyperlipoproteinemia Type IV / genetics
  • Hyperlipoproteinemia Type IV / metabolism
  • Hyperlipoproteinemia Type IV / pathology
  • Hypertriglyceridemia / diagnosis*
  • Hypertriglyceridemia / genetics
  • Hypertriglyceridemia / metabolism
  • Hypertriglyceridemia / pathology
  • Insulin / genetics
  • Lipoprotein Lipase / genetics
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Receptors, Lipoprotein / genetics
  • Triglycerides / genetics

Substances

  • ANGPTL3 protein, human
  • APOA5 protein, human
  • Angiopoietin-Like Protein 3
  • Angiopoietin-like Proteins
  • Apolipoprotein A-II
  • Apolipoprotein A-V
  • Apolipoprotein C-II
  • Apolipoproteins B
  • GPIHBP1 protein, human
  • Insulin
  • LMF1 protein, human
  • Membrane Proteins
  • Receptors, Lipoprotein
  • Triglycerides
  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • LPL protein, human
  • Lipoprotein Lipase