Mutations in HFE causing hemochromatosis are associated with primary hypertriglyceridemia.

Context: Most cases of primary hypertriglyceridemia (HTG) are caused by the interaction of unknown polygenes and environmental factors. Elevated iron storage is associated with metabolic syndrome, diabetes, and obesity, and all of them are associated with HTG.

Objective: The aim of the study was to analyze whether HFE mutations causing hereditary hemochromatosis (HH) are associated with primary HTG.

Design: Genetic predisposition to HH was analyzed in a case-control study.

Setting: The study was conducted at University Hospital Lipid Clinic.

Participants: We studied two groups: 1) the HTG group, composed of 208 patients; and 2) the control group, composed of 215 normolipemic subjects and 161 familial hypercholesterolemia patients.

Intervention: Two HFE mutations (C282Y and H63D) were analyzed.

Main Outcome Measure: We measured HH genetic predisposition difference between groups.

Results: HH genetic predisposition was 5.9 and 4.4 times higher in the HTG group than in the normolipemic (P = 0.02) and FH (P = 0.05) subjects, respectively. There were 35 cases (16.8%) of iron overload in the primary HTG group, 14 (6.5%) and nine (5.6%) in the normolipidemic and FH groups, respectively. A higher HH genetic predisposition and a different prevalence of iron overload in subjects with HH genetic predisposition among groups contributed to this higher prevalence. None of the four cases with the HFE genotype associated with high risk of HH in the control groups presented iron overload; however, in eight of 11 subjects (72.7%) with primary HTG and HH genetic predisposition, the iron overload was present.

Conclusion: Mutations in HFE gene, favoring iron overload and causing HH, could play an important role in the development of several phenotypes of primary HTG.