BACKGROUND AND AIMS: Familial hypertriglyceridemia (FHTG) is a partially characterized primary dyslipidemia which is frequently confused with other forms hypertriglyceridemia. The aim of our study is to search for specific features that help clinicians in the recognition of FHTG.
APPROACH: We included 84 FHTG cases, 728 subjects with mild-to-moderate hypertriglyceridemia (CHTG) and 609 normotriglyceridemic controls for genetic, clinical and biochemical assessment. A set of 53 SNPs previously associated to TG levels, as well as 37 rare variants within the main five genes associated to hypertriglyceridemia (i.e. LPL, APOC2, APOA5, LMF1 and GPIHBP1) were analyzed. A panel of endocrine regulatory proteins closely related to triglycerides homeostasis were compared between FHTG and CHTG.
RESULTS: Compared to CHTG, FHTG subjects had higher HOMA-IR, apolipoprotein AII, FGF21, ANGPTL3 and ANGPTL4 concentrations and lower HOMA-B%, apolipoprotein B and leptin. The polygenic set of SNPs, previously associated with triglyceride levels, accounted for 1.78% of the explained variance of triglyceride levels in FHTG and 6.73% in CHTG.
CONCLUSION: 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, FGF21, ANGPTL3, apoAII and lower levels of apoB. We propose the inclusion of these analytes as useful markers to distinguish FHTG from other causes of hypertriglyceridemia.