Mutations in HFE causing hemochromatosis are associated with primary hypertriglyceridemia

Area of Science:

• Genetics and Metabolism
• Cardiovascular Disease Research

Background:

• Primary hypertriglyceridemia (HTG) often results from complex gene-environment interactions.
• Elevated iron storage is linked to metabolic syndrome, diabetes, and obesity, conditions associated with HTG.

Purpose of the Study:

• To investigate the association between HFE gene mutations, causative of hereditary hemochromatosis (HH), and primary HTG.
• To analyze the role of genetic predisposition to HH in the development of HTG.

Main Methods:

• A case-control study was conducted at a University Hospital Lipid Clinic.
• Two groups were analyzed: 208 patients with primary HTG and a control group comprising 215 normolipemic subjects and 161 familial hypercholesterolemia patients.
• Genetic predisposition to HH was assessed by analyzing two HFE mutations (C282Y and H63D).

Main Results:

• HH genetic predisposition was significantly higher in the HTG group (5.9 times) compared to normolipemic subjects and (4.4 times) compared to familial hypercholesterolemia patients.
• Iron overload was more prevalent in the primary HTG group (16.8%) than in normolipemic (6.5%) and familial hypercholesterolemia (5.6%) groups.
• In subjects with HH genetic predisposition, iron overload was present in 72.7% of primary HTG patients versus none in the control groups.

Conclusions:

• HFE gene mutations, which promote iron overload and cause HH, may play a significant role in the pathogenesis of various primary HTG phenotypes.
• The findings suggest a potential link between iron metabolism dysregulation and hypertriglyceridemia.