MTHFR Gene Polymorphism in Indigenous Populations of Siberia in Relation to Sensitivity to Mercury

This study analyzes the polymorphism of exons of the MTHFR gene, which encodes 5,10-methylenetetrahydrofolate reductase, a key enzyme involved in folate and methionine metabolism, in indigenous Siberian populations. The analysis of allele and haplotype distributions for the polymorphic loci rs2274976, rs1801131, rs2066462, rs1801133, and rs2066470 revealed the presence of interregional differences among indigenous population of Siberia. A more detailed analysis was performed for loci rs2274976, rs1801131, and rs1801133, nucleotide substitutions in which lead to a decrease in the MTHFR enzyme activity. In addition, according to published data, Canadian Inuit individuals, carriers of the rs2274976-T, rs1801131-G, and rs1801133-G variants, have elevated mercury concentrations in the blood, which can be associated with the peculiarities of traditional Arctic diet containing relatively high levels of toxic metals. Our population genetic analysis revealed an increase in the frequency of the TGG haplotype (at the above indicated loci) from southern to northeastern Siberia, with maximum frequency values in Eskimo populations. The reasons for the identified dynamics of MTHFR gene haplotype distribution in indigenous Siberian populations are discussed, including a possibility of evolutionary compromise related to the protection against mercury neurotoxicity in Arctic populations.