Analysis of haemochromatosis gene mutations in a population from the Mediterranean Basin

Background/Aims: The C282Y mutation in the haemochromatosis gene (HFE) loca ted on chromosome 6 has been identified as the main genetic basis of heredi tary haemochromatosis (HH). Two more mutations of that gene, H63D and S65C, appear to be associated with milder forms of HH. A high allele frequency f or C282Y and H63D mutations was reported in populations from North Europe, while incomplete information is available for individuals from the Mediterr anean Basin where C282Y homozygotes comprise a smaller percentage of HH cas es. In this study we investigated the allele frequency of HFE mutations and the association between HFE mutations and cases of HH in a population from the South of Italy (Sicily and Calabria). In addition, we evaluated a poss ible association between HFE mutations and either chronic liver disease or type II diabetes. Patients and Methods: Three hundred and twenty-seven indi viduals (654 chromosomes) were tested for C282Y, H63D and S65C mutations of the HFE gene by restriction fragment length polymorphism. Four had HH, 23 had hepatocellular carcinoma, 100 had chronic liver disease, 100 had type I I diabetes, and 100 were healthy controls. Results: Both C282Y and S65C mut ations were each detected in one of the 654 chromosomes analysed (allele fr equency=0.15%), while H63D change was found in 122 chromosomes (allele freq uency=18.6%) and was equally distributed in all the categories examined. On e healthy individual had compound heterozygosity for C282Y and H63D mutatio ns. The frequency of C282Y in this Southern Italian sample was the lowest y et reported for a population of European origin. None of the four HH patien ts was either homozygous or heterozygous for C282Y. Conclusions: In Mediter ranean populations from Southern Italy the C282Y mutation occurs sporadical ly and HFE polymorphisms seem to have little diagnostic relevance.