ELEMENTS OF ETIO-PATHOGENESIS OF HYPERHOMOCYSTEINEMIA IN CHILDREN LIVING IN THE REGIONS AFFECTED FROM THE ACCIDENT AT THE CHERNOBYL NUCLEAR POWER PLANT
Authors:   Ecology and Health Coordination and Analytical Centre, Ukraine, Bandazheuski Yuri , Dubovaya Nataliia ,   Ecology and Health Coordination and Analytical Centre, Ukraine
Published: May 2023

The prevalence of hyperhomocysteinemia in the population of children living in the area affected by the accident at the Chernobyl Nuclear Power Plant (ChNPP) requires a deep study of the etio-pathogenesis of metabolic disorders of the sulfur-containing amino acids methionine (Met) and homocysteine (Hcy) under radiation exposure. The purpose of the study was to assess the involvement of genetic (folate cycle polymorphisms – FC) and environmental factors in the occurrence of hyperhomocysteinemia in boys and girls living in the Ivankovsky and Polessky districts of the Kyiv region of Ukraine, near the Chernobyl Exclusion Zone (ChEZ). The methodology of the study is based on the evaluation by statistical methods of the results of genetic and laboratory examinations of 690 children (368 girls and 322 boys), aged 8-17 years, obtained in the course of projects of the European Commission, the Regional Council of Rhone-Alpes (France) and the French public organization "Children Chernobyl". It has been shown that in most cases, the violation of Hcy metabolism and the occurrence of hyperhomocystinemia in children from areas affected by the Chernobyl accident are caused by the association of genotypes with risk alleles of MTHFR:C677T and MTRR:A66G polymorphisms. Given the wide prevalence in the population, combinations of their heterozygous forms are of the greatest importance.The risk allele G of the MTRR:66 polymorphism also has a negative effect on the processes of Hcy methylation when associated with the risk allele G of the MTR:A2756G polymorphism and with compound heterozygosity A/CMTHFR:1298 – C/TMTHFR:677. In the body of boys, compared with the body of girls, combinations of risk alleles for FC polymorphisms are manifested by a more pronounced disturbance of Hcy metabolism. The A/AMTRR:66 genotype promotes Hcy utilization in the transsulfuration cycle, even if only one C allele of the MTHFR:677 polymorphism functions.An external environmental factor in the form of radioactive agents incorporated into vital organs, undermining cellular energy, has a negative impact on the processes of cobalamin methylation. The consequence of this is the occurrence of a state of hyperhomocysteinemia in more than 50 % of boys and girls who do not have risk alleles of MTR:A2756G, MTHFR:C677T and MTRR:A66G polymorphisms in the genome. Conclusions. The main internal cause of hyperhomocysteinemia in children living near the ChEZ is the association of risk alleles for FC genetic polymorphisms.The combined effect of endogenous (genetic mutations of FC) and exogenous (radioactive elements, their decay products, substances formed during the combustion of wood) factors leads to disruption of the Hcymethylation process and the emergence of a state of hyperhomocysteinemia in children living in the territory affected by the Chernobyl accident. This type of metabolic disorder can be considered a distant consequence of the Chernobyl accident. Further research should be aimed at developing measures for the prevention and treatment of hyperhomocysteinemia, as a condition associated with the occurrence of serious pathological processes.