Liver 2001: 21: 233–236 Copyright C Munksgaard 2001 Printed in Denmark . All rights reserved Liver ISSN 0106-9543 Analysis of haemochromatosis gene mutations in a population from the Mediterranean Basin Campo S, Restuccia T, Villari D, Raffa G, Cucinotta D, Squadrito G, Salvatore Campo*, Tea Restuccia*, Pollicino T, Raimondo G. Analysis of haemochromatosis gene mutations Daniela Villari 1 , Giuseppina Raffa, in a population from the Mediterranean Basin. Domenico Cucinotta, Liver 2001: 21: 233–236. C Munksgaard, 2001 Giovanni Squadrito, Teresa Pollicino and Giovanni Raimondo Abstract: Background/Aims: The C282Y mutation in the haemochroma- Dipartimento di Medicina Interna and tosis gene (HFE) located on chromosome 6 has been identified as the main 1 Dipartimento di Patologia Umana, Universita ` di genetic basis of hereditary haemochromatosis (HH). Two more mutations Messina, Messina, Italy of that gene, H63D and S65C, appear to be associated with milder forms of HH. A high allele frequency for C282Y and H63D mutations was re- ported in populations from North Europe, while incomplete information is available for individuals from the Mediterranean Basin where C282Y homozygotes comprise a smaller percentage of HH cases. In this study we investigated the allele frequency of HFE mutations and the association be- tween HFE mutations and cases of HH in a population from the South of Italy (Sicily and Calabria). In addition, we evaluated a possible association between HFE mutations and either chronic liver disease or type II dia- betes. Patients and Methods: Three hundred and twenty-seven individuals (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 II diabetes, and 100 were healthy controls. Results: Both C282Y and S65C mutations were each detected in one of the 654 chromosomes ana- lysed (allele frequencyΩ0.15%), while H63D change was found in 122 Key words: diabetes – ethnic origin – HFE – liver chromosomes (allele frequencyΩ18.6%) and was equally distributed in all diseases – polymorphism the categories examined. One healthy individual had compound hetero- Giovanni Raimondo, Dipartimento di Medicina zygosity for C282Y and H63D mutations. The frequency of C282Y in this Interna, Policlinico Universitario – 98124 Southern Italian sample was the lowest yet reported for a population of Messina – Italy. European origin. None of the four HH patients was either homozygous Tel: 39 (0)90 2212392. Fax: 39 (0)90 2935162. e-mail:raimondo/unime.it or heterozygous for C282Y. Conclusions: In Mediterranean populations from Southern Italy the C282Y mutation occurs sporadically and HFE Received 23 June 2000, accepted 15 February polymorphisms seem to have little diagnostic relevance. 2001 Hereditaryhaemochromatosis (HH) is an in- herited disorder of iron metabolism common in northern European populations (1–4). Mutations of the haemochromatosis gene ( HFE) located on chromosome 6 have been identified as the genetic basis of HH.In particular,homozygosity for the C282Y mutation and compound heterozygosity for C282Y and H63D mutations account for the vast majority of HH cases (5–9). More recently, an S65C substitution has been found to be associated *S.C. and T.R. equally contributed to this work. 233 with a significantly increased risk of developing a milder form of haemochromatosis (10). In ad- dition,it has been suggested that HFE mutations may be involved both in cases of liver disease of differentaetiology complicated by iron overload and in cases of type II diabetes (11–13). Extensive epidemiological studies have shown a very high allele frequency for C282Y and H63D mutationsamongpopulationsof Celtic origin from Northern Europe,while incomplete infor- mation is availablefor individualsof Southern European origin, and in particular in populations from the MediterraneanBasin wherehaemo-