Introduction

Once considered to be a rare disorder, hemochromatosis is now recognized as the most common known autosomal recessive disorder in Caucasians, which occurs commonly in many European or European-derived populations. The major factor leading to this recognition was the clarification of its genetic mode of transmission. The finding by Simon and co-workers of the association of hemochromatosis with the MHC class I antigen HLA-A3 and the subsequent demonstration of the haplotypic nature of that association marked the beginning of a new era in the clarification of the true frequency of hemochromatosis. Assignment of a genotype on the basis of HLA typing has permitted an estimate of frequencies of the disorder in several areas of the world that are greater than the calculations previously based on the identification of clinical symptoms or on the findings of autopsy studies. The recent finding by Feder and co-workers of the HFE gene, one mutation which accounts for the majority of hemochromatosis patients, permits a new approach to the study of the epidemiology of the disorder. In spite of the frequency of hemochromatosis in most Caucasian populations, there is considerable variation in its prevalence among different countries and even within national boundaries. This chapter provides an overview of the geographical variations of the HLA phenotypes marking the HFE gene and of the HFE genotypes found in hemochromatosis patients and normal populations throughout the world, and offers some explanations for the variations observed.