Polymorphism of the genes encoding for the carnitine acyltransferases in native populations of Siberia

Background. Exome polymorphism is a rich source of information on the structure and function of proteins and metabolic pathways. The traditional diet of native populations of Northeast Asia (Eskimos, Chukchi and Koryaks) is enriched with fatty acids, which presupposes the existence of adaptive rearrangements of the lipid metabolism system among northern aborigines. Carnitine acyltransferases are the most important group of enzymes that metabolize fatty acids. Materials and methods. To study adaptive changes in the genes encoding for the carnitine acyltransferases, we performed a screening of polymorphisms in the exons of CPT1A, CPT1B, CPT1C, CPT2, CRAT, and CROT genes in various populations of native inhabitants of Siberia. Results. In exons of five genes (with the exception of CROT), 16 non-synonymous substitutions were identified. Of these, three substitutions were detected at high frequencies in populations of Northeast Asia (in Eskimos, Chukchi and Koryaks): at the loci rs80356779 of the CPT1A gene (replacement of P479L) and rs763273578 of the CPT1C gene (T740A), as well as a new polymorphism at position 131866581 of chromosome 9 at the CRAT gene (S99F). Exome analysis showed that among native populations of Northeast Asia, new non-synonymous substitutions with high pathogenicity indices appeared in the genes of energy metabolism and lipid exchange (genes GK2, ABHD6, NCOA2, OSPL3, LRP10, TTN, and PTTG2). Conclusion. It is assumed that new variants of non-synonymous polymorphism arose as a result of genetic adaptation of native peoples to the extremely cold climate and a specific “Arctic” diet of aborigines of the Far North.