Toxic metals and genetic polymorphism in indigenous populations of northern Asia and America.

The polymorphism of genes encoding enzymes involved in heavy metal metabolism was analyzed in indigenous Siberian populations based on the mercury, lead, and cadmium contents in the blood of Canadian Inuit carrying different genotypes. Additionally, we examined the polymorphism of genetic loci associated with sensitivity to arsenic exposure in indigenous Siberian populations using data on inorganic arsenic content in the urine of indigenous Andean populations who had consumed drinking water with elevated arsenic levels for thousands of years. A population genetic approach was used to seek genetic markers of toxic metal exposure in humans by analyzing genetic differences between populations living in different natural environments and under different conditions of toxic element contamination. Statistically significant differences were primarily observed between indigenous populations in Northeast Siberia (Siberian Eskimo (Yupik), Chukchi, and Koryaks) and samples from the central (Evens, Evenki, and Yakuts) and southern (Altaians, Shors, and Buryats) regions of Siberia. The maximum population branch statistics (PBS) values, which indicate the probable effect of selection on genetic loci sensitive to mercury exposure, were identified in seven gene loci: MTHFR (rs2274976 and rs1801131), GPX4 (rs713041), ABCB1 (rs1128503), AHR (rs2066853), TXNRD2 (rs5748469), and SEPHS2 (rs1133238). Loci rs713041 (GPX4), rs7483 (GSTM3), and rs2282143 (SLC22A1) can be considered genetic markers of lead exposure. Loci rs2274976 (MTHFR) and rs1056836 (CYP1B1) provide information about cadmium distribution in blood. It was found that protective variants of the AS3MT gene polymorphism are widespread (65.8 %) in the indigenous populations of Northeast Siberia. This is despite the lack of information regarding the long-term consumption of arsenic-contaminated drinking water by indigenous peoples along the Chukotka and Priokhotye coasts. It is hypothesized that seafood, which constitutes the core of the traditional "Arctic" diet of the indigenous populations inhabiting the coastal regions of the northern seas, may potentially be a significant source of arsenic and other toxic elements in Northeast Siberia. Further molecular, biochemical, and toxicological studies are necessary to elucidate the mechanisms by which toxic metals impact the genetic structure of indigenous populations in the Far North over long periods of time.