Mutations in HFE causing hemochromatosis are associated with primary hypertriglyceridemia.
BACKGROUND
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.


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


METHODS
The study was conducted at University Hospital Lipid Clinic.


METHODS
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.


METHODS
Two HFE mutations (C282Y and H63D) were analyzed.


METHODS
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.


CONCLUSIONS
Mutations in HFE gene, favoring iron overload and causing HH, could play an important role in the development of several phenotypes of primary HTG.
Solanas-Barca
María
M
Unidad de Lípidos and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS), 50009 Zaragoza, Spain.
Mateo-Gallego
Rocío
R
Calmarza
Pilar
P
Jarauta
Estíbaliz
E
Bea
Ana M
AM
Cenarro
Ana
A
Civeira
Fernando
F
D000328:Adult; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006432:Hemochromatosis / Q000097:blood / Q000150:complications / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D015995:Prevalence; D012016:Reference Values
D008076:Cholesterol, HDL; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D000960:Hypolipidemic Agents; D008565:Membrane Proteins