Unique genetic profile of hereditary hemochromatosis in Russians: High frequency of C282Y mutation in population, but not in patients

Hereditary hemochromatosis (HH) is a common cause of primary iron overload induced by genetic impairment of iron metabolism. More than 80% of HH patients in populations of European origin are homozygotes for a single mutation C282Y, or compound heterozygotes for C282Y and H63D mutations in the HFE gene. However, in the majority of Asian, African, Australasian, and Amerindian populations, frequencies of C282Y are close to zero. Data on the prevalence of HFE mutations in Russian population and in Russian patients with HH are very limited. In this work, we determined frequencies of C282Y and H63D in ethnical Russians living in the Central European region of Russia. Furthermore, we tested whether homozygocity for C282Y is the major cause of HH in Russians. We found that, in the Russian population, the frequency of C282Y mutation in the HFE gene is relatively high and corresponds to mean European levels. However, in contrast to the majority of European populations, homozygocity for C282Y is found only in a small proportion (5%) of patients with biochemical and clinical signs of HH. These data suggest that either the penetrance of C282Y in Russia is lower than in Western countries, or that a more frequent non-HFE dependent mechanism of primary iron overload dominates in Russian population.