Polymorphism of candidate genes for the formation of "polar stress syndrome" in children living in the circumpolar territory of Eastern Siberia (using the example of ANKK1/DRD2 (rs18004976) and TNF (rs1800629))
Authors:   MD, Professor, Academician of the Russian Academy of Sciences, Scientific Director of FBSI  Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Zaitseva N.V. , Dolgikh O.V. ,   MD, Head of the Department of Immunobiological Diagnostics of FBSI Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Nikonoshina N.A. ,   junior research assistant of Department of Immunobiological Diagnostics, postgraduate student of the FBSI Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Alekseev V.B. ,   MD, Professor, Director of FBSI Federal Scientific Center for Medical and Preventive Health Risk Management Technologies
Published: January 2025

"Polar stress syndrome" is the result of a negative extreme climatic and geographical conditions impact in the circumpolar territories with the subsequent formation of maladaptation disorders of immune and nervous regulation. There is no doubt the relevance of studying the SNP features of candidate ANKK1/DRD2 (rs18004976) and TNF (rs1800629) genes in the aspect of identifying probable predisposition markers to the "polar stress syndrome" development in the circumpolar territory population. The aim is to study the features of polymorphism of immune and nervous systems regulatory genes as possible markers of predisposition to the "polar stress syndrome" formation in the children population of circumpolar territory by the example of the dopamine receptor ANKK1/DRD2 (rs18004976) and the tumor necrosis factor TNF (rs1800629) genes. Materials and methods. 717 children aged 7-13 years were examined. 136 people live in conditions conducive to the formation of "polar stress syndrome" (circumpolar territory); 581 people live in the middle latitude territories. The identification of apoptosis receptors CD3+CD95+ and TNFR was carried out by flow cytofluorometry, dopamine production was analyzed by ELISA. The SNP of ANKK1/DRD2 (rs18004976) and TNF (rs1800629) genes were identified by real-time PCR. Results. The results of children genotyping established the reliable association of the T-allele and TT-genotype of the ANKK1/DRD2 gene (rs18004976) with dopamine hyperproduction and the similar relation of the G-allele and GG-genotype of the TNF (rs1800629) gene with an excessive content of TNFR and CD3+CD95+ lymphocytes (p<0.05). Overexpression of TNFR, CD3+CD95+ and dopamine in children was significantly associated with T-allele and TT-genotype of the ANKK1/DRD2 gene (rs18004976) and G-allele and GG-genotype of the TNF gene (rs1800629) relative to the CC-genotype of the ANKK1/DRD2 (rs1800497) gene and AA-genotype of TNF (rs1800629) gene independently of the analyzed sample (p<0.05) and reached the maximum values in carriers of the TT-genotype of the ANKK1/DRD2 (rs18004976) gene and GG-genotypes of TNF (rs1800629) gene in the observation group. Moreover, the difference in the allele and genotype frequency distribution of candidate genes between analyzed groups was significant (TT-genotype of the ANKK1/DRD2 gene (rs18004976) (OR=2.43; 95% CI=1.43-4.15; p=0.04); GG-genotype of the TNF gene (rs1800629) (OR=1.66; 95% CI=1.02-2.70; p=0.03)), which verified the contribution of genetic predisposition to the development of "polar stress syndrome" in children in extreme climatic and geographic conditions of the circumpolar territory.
Keywords: "polar stress syndrome", children, dopamine, apoptosis, genetic polymorphism, candidate genes.