Participation of homocysteine in the regulation of thyroid hormone metabolism in children living near the Сhоrnobyl nuclear power plant

Abstract

The negative role of homocysteine (Hcy) in the occurrence of a number of severe diseases leading to death or disability has been established. However, the cause-and-effect mechanisms have not been determined. The implementation of projects of the European Commission and the Rhone-Alpes Council (France) in Ukraine (2013-2017) made it possible to identify elevated Hcy blood levels in 70.0% of cases, as well as structural and functional changes in the thyroid gland (TG) and correlations between Hcy and hormones of the pituitary-thyroid axis in a group of adolescents living near the Chоrnobyl Nuclear Power Plant (CNPP). To understand the pathogenetic mechanisms of pathological processes associated with Hcy and the thyroid gland, the present study was conducted, the aim of which was a comprehensive assessment of the participation of Hcy in the regulation of thyroid hormone metabolism in children living near the Chоrnobyl Exclusion Zone (ChEZ) in Ivankivskyі district of Kyivskyі region. Research methods. An analytical study was conducted using statistical indicators obtained during laboratory and genetic examination of 178 children aged 12-17 years old from settlements bordering the ChEZ. To assess the regulatory processes under study, a correlation analysis was performed between the indicators Hcy, thyroid hormones, pituitary thyroid stimulating hormone (TSH), vitamins B9, B12, B6, taking into account various combinations of alleles of genetic polymorphisms of the folate cycle (FC). Results. In the body of most children living in the area affected by the Chornobyl accident, near the ChEZ, the level of Hcy in the blood exceeds the physiological level. It is shown that the concentration of vitamins B9 and B12 in the blood reflects the ability of FC enzymes to methylate Hcy. The homozygous variant of the T allele MTHFR:677 in the genome of children reduces the content of active forms of vitamin B9 and increases the content of Hcy in the blood. In the case of the homozygous variant of the G allele MTR:2756, the process of formation of the active form of B12 is disrupted, which entails activation of the transsulfuration reaction cycle and a decrease in the Hcy level in the blood. Increased Hcy content in the blood induces the synthesis of TSH, which is involved in the process of T4 deiodination and the formation of T3. The level of T4 in the blood depends on how this metabolite is used by peripheral organs and tissues and indicates what the energy needs of the body are. Peripheral organs, including the liver and kidneys, are responsible for the utilization of T4 and the formation of T3 - the active form of thyroid hormones. T3 has a stimulating effect on FC enzymes, which leads to increased methylation of Hcy and an increase in the formation of internal methionine. At the same time, it blocks the utilization of Hcy in the transsulfuration reaction cycle. Conclusions. In children developing under conditions of constant radiation exposure, the FC enzyme system plays an important role in the formation of regulatory connections between the pituitary gland and the thyroid gland. It has been proven that T3 maintains the required concentration of Hcy in the body, increasing the formation of the active form of vitamin B9. The effect of T3 on FC is expressed in heterozygous variants of the risk alleles of the MTR:2756, MTHFR:677 polymorphisms. The radiation factor, in the form of radionuclides incorporated into the body, has a negative effect on the Hcy methylation process, causing a state of hyperhomocysteinemia in adolescents living near the ChEZ, regardless of the state of the FC genes.