The ethnospecific distribution of the HFE haplotypes for IVS2(+4)t/c, IVS4(-44)t/c, and IVS5(-47)g/a in populations of Russia and possible effects of these single-nucleotide polymorphisms in splicing.

AIM: The aim of this work was a haplotype analysis of the major mutations (C282Y, H63D, S65C) and IVS2(+4)t/c, IVS4(-44)t/c, and IVS5(-47)a/g polymorphisms of the hemochromatosis HFE gene in populations inhabiting the territories of Russia (Russians, Finno-Ugrians, Central Asians, and Arctic Mongoloids). METHOD: The hemochromatosis gene (HFE) alleles were detected using the polymerase chain reaction/restriction fragment length polymorphism method. RESULTS: Of the eight possible intronic haplotype variants, the TTG, TTA, CTA, and CCA were identified. The HFE alleles with the different haplotype variants were distributed in an ethnospecific manner among the populations. Our finding was that every one of the C282Y, H63D, and S65C mutations was in linkage disequilibrium only with one of the intronic haplotype variants: TTG, CTA, and CCA, respectively. The data from context analysis of DNA regions where the examined single-nucleotide polymorphisms are located suggested their involvement in splicing. CONCLUSIONS: Different genotypes of the HFE gene occur at different frequencies among populations of Russia. Carriers of the specific genotype variants may potentially express distinct sets of alternative HFE mRNAs.