Increased susceptibility to nonalcoholic fatty liver disease in heterozygotes for the mutation responsible for hereditary hemochromatosis.
BACKGROUND
Insulin resistance is a key feature of nonalcoholic fatty liver disease. Patients with hereditary hemochromatosis, a disease characterized by progressive iron overload due, in most cases, to homozygosity for C282Y mutation in the HFE gene, have often decreased insulin sensitivity and release.


OBJECTIVE
To determine whether increased iron parameters/heterozygosity for the mutations of the HFE gene confer susceptibility to nonalcoholic fatty liver disease.


METHODS
One hundred and thirty-four consecutive Italian patients with clinical and ultrasonographic diagnosis of nonalcoholic fatty liver disease (82 with hyperferritinemia), half confirmed by liver biopsy.


METHODS
Insulin was determined by radioimmunoassay. HFE gene mutations were determined by polymerase chain reaction and restriction fragment length polymorphism analysis.


RESULTS
(1) Prevalence of C282Y HFE mutation was significantly higher in patients with nonalcoholic fatty liver disease compared to controls, the difference being more striking in patients with hyperferritinemia than in those without. (2) The presence of mild iron overload was associated with a lower insulin release. (3) Carriers of C282Y mutation developed nonalcoholic fatty liver disease despite lower body mass index and triglycerides.


CONCLUSIONS
The mild iron overload associated with heterozygosity for C282Y HFE mutation confers susceptibility to nonalcoholic fatty liver disease, causing relative insulin deficiency.
Valenti
L
L
Department of Internal Medicine, Ospedale Maggiore IRCCS, University of Milan, Milan, Italy.
Dongiovanni
P
P
Fracanzani
A L
AL
Santorelli
G
G
Fatta
E
E
Bertelli
C
C
Taioli
E
E
Fiorelli
G
G
Fargion
S
S
D000328:Adult; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005293:Ferritins / Q000378:metabolism; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D019190:Iron Overload / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D014168:Transferrin / Q000378:metabolism
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D005293:Ferritins