Objective: To determine the relevance of C282Y and H63D mutations of HEF gene in patients with iron overload.
Patients and methods: Patients with iron overload referred to our Liver Unit were included in the study. The association of mutations to different diagnosis and their impact on the severity of the hepatopathy were explored. Sensitivity, specificity and positive and negative predictive values of mutations for the diagnosis of haemochromatosis were determined.
Results: The study included 78 patients with iron overload. The control group included 21 patients of similar age and sex ratio without iron overload nor hepatopathy. Twenty three patients had haemochromatosis, 22 alcoholic liver disease and 33 other diseases unrelated to iron metabolism. Seventy three per cent of patients with haemochromatosis were homozygous for the C282Y mutation. All the C282Y homozygous subjects had also haemochromatosis. Fifty three per cent of patients with alcoholic hepatopathy had some kind of mutation. This has been also observed in 70% of patients with iron-unrelated diseases. Such percentage was significantly greater than in the control group (24% with H63D mutation). C282Y homozygosity in patients with iron overload had a sensitivity of 73.9%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 89.6%.
Conclusions: In our population, as in all the Western countries, haemochromatosis is mainly associated to homozygous C282Y mutation. The high frequency of mutations in patients with iron overload and without haemochromatosis suggests the involvement of such mutations in iron overload.