HYPERHOMOCYSTEINEMIA AND PITUITARY-THYROID AXIS AMONG CHILDREN LIVING NEAR THE CHORNOBYL EXCLUSION ZONE
Authors:   Ecology and Health Coordination and Analytical Centre, Ukraine, Bandazheuski Yuri , Dubovaya Nataliia ,   Ecology and Health Coordination and Analytical Centre, Ukraine
Published: November 2023

The prevalence of cases of hyperhomocysteinemia in the population of children living in a radioactively contaminated area due to the accident at the Chornobyl Nuclear Power Plant (ChNPP) requires an in-depth and immediate study of the aetiopathogenesis of this condition. In view of the increase in the number of cases of thyroid cancer in the period following the accident, it is advisable to determine the relationship between the level of homocysteine (Hcy), the state of the folate cycle (FC) and the thyroid status in children. The aimof the study was to determine the association of Hcy and pituitary-thyroid axis hormones with a different combination of genetic polymorphisms of FC in children living in areas bordering the Chornobyl 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 336 individuals aged 12-17 from the Ivankiv and Poliske districts of the Kyiv Oblast of Ukraine, obtained during the implementation of projects of the European Commission and the Regional Council of the Rhone-Alpes (France). Blood levels of pituitary thyroid stimulating hormone (TSH), free triiodothyronine (T3), free thyroxine (T4), Hcy, vitamins B6, B9 and B12 were analysed, and the status of the genetic system of FC was studied. Results. It was shown that in subgroups of children from the Ivankiv district with dysfunction of the main enzymes of FC due to risk alleles of genetic polymorphisms MTR:A2756G, MTHFR:A1298C, MTHFR:C677T and MTRR:A66G, after forest fires in the ChEZ, contributing to an increase in blood Hcy content, direct correlations between Hcy and TSH were revealed. The formation of the analysed subgroups including the genotypes of different FC polymorphisms made it possible to detect stronger correlations between Hcy and TSH compared to subgroups in which only the genotypes of one polymorphism were taken into account as the main ones. At the same time, it was possible to determine the metabolic relationships of sulphur-containing amino acids and the pituitary-thyroid axis in the children's bodies, taking into account the state of the FC genes and environmental exposure, including the radiation factor. The strongest direct relationship between Hcy and TSH was found in the compound heterozygous association A/C MTHFR:1298 – C/T MTHFR:677 in combination with genotypes containing risk alleles of the genetic polymorphisms MTR:A2756G and AMTRR:A66G. At the same time, transsulfuration reactions using Hcy were activated. Hcy, which promotes the formation of TSH, plays an important role in the regulation of thyroid hormone production. TSH stimulates the process of deiodination of T4 in tissues, resulting in increased production of T3. T3, acting on MTHFR, stimulates the formation of 5-MTHF, which is involved in the process of Hcy methylation. With increased formation, T3 inhibits the activity of trans-sulfurisation reactions. Conclusions. According to the results of the study, the cycle of trans-sulphurisation reactions should be considered as a metabolic mechanism linking thyroid hormone formation and the exchange of sulphur-containing amino acids. The relationship between hyperhomocysteinemia and the pituitary-thyroid axis in children of the Ivankiv district illustrates the compensatory-adaptive reaction of the developing organism aimed at increasing Hcy methylation under appropriate endogenous (the state of the genetic apparatus of the FC) and exogenous (radiation exposure) conditions.