Научная статья на тему 'The state of folate metabolism and its link with thyroid system in children after forest fires in the Chornobyl exclusion zone'

The state of folate metabolism and its link with thyroid system in children after forest fires in the Chornobyl exclusion zone Текст научной статьи по специальности «Фундаментальная медицина»

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Ключевые слова
folate metabolism / homocysteine / hormones of hypophysis and thyroid gland / forest fires / Chоrnobyl exclusion zone. / фолатний цикл / гомоцистеїн / гормони гіпофіза і щитоподібної залози / лісові пожежі / Чорнобильська зона відчуження.

Аннотация научной статьи по фундаментальной медицине, автор научной работы — Bandazhevskyi Yu. I., Dubova N. F.

Objective.We determined the state of folate cycle and its link with thyroid system in the children of the Ukrainian Polissia after forest fires in the Chornobyl exclusion zone. Methods: Immunochemical, mathematical and statistical ones. Results. Blood homocysteine levels were statistically significantly higher in the subgroup of the children who were the carriers of the T risk allele of the MTHFR:С677Т genetic polymorphism living in Ivankovsky and Poliskyi districts than in the subgroup of the children without this allele. The examination of the children from the regions adjacent to the Chornobyl nuclear power plant allowed to identify in them the metabolic processes’ changes in the form of increased production of Нс due to the forest fires in the exclusion zone. Blood Hс levels were higher in the children from Ivankivskyi district examined after fires in the Chornobyl exclusion zone than in those from Poliskyi district examined before fires, including the majority of genetic subgroups, with the exception of the genetic subgroup which included cases of homozygous carriership of the T allele. Direct links between blood homocysteine and pituitary thyroid-stimulating hormone levels, homocysteine and triiodothyronine levels were detected in the group of the children from Ivankivskyi district who had higher blood homocysteine concentrations compared to the group of children from Poliskyi district. Сonclusions. It can be reasonably assumed that fires in the Chornobyl exclusion zone have a negative effect on the functioning of folate metabolism in a child’s organism

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СТАН ФОЛАТНОГО ЦИКЛУ ТА ЙОГО ЗВ'ЯЗОК З ТИРЕОЇДНОЮ СИСТЕМОЮ У ДІТЕЙ ПІСЛЯ ЛІСОВИХ ПОЖЕЖ У ЧОРНОБИЛЬСЬКІЙ ЗОНІ ВІДЧУЖЕННЯ

Мета дослідження: визначення стану фолатного циклу та його зв'язку з тиреоїдною системою у дітей українського Полісся після лісових пожеж у Чорнобильській зоні відчуження. Методи дослідження. Імунохімічний, математико-статистичний. Результати. У підгрупі дітей-носіїв алелі ризику Т генетичного поліморфізму MTHFR:С677Т, які проживають в Іванківському і Поліському районах, рівень гомоцистеїну у крови був достовірно вищим, ніж у підгрупі дітей, позбавлених даної алелі. Обстеження дітей із районів, прилеглих до Чорнобильської атомної електростанції, дозволило виявити у них зміни метаболічних процесів у вигляді підвищеної продукції гомоцистеїну у зв'язку з лісовими пожежами у зоні відчуження. У групі дітей із Іванківського району, обстежених після пожежі у Чорнобильській зоні відчуження, рівень гомоцистеїну у крови вищий, ніж у групі дітей із Поліського району, обстежених до пожежі, у тому числі у більшості генетичних підгруп, за винятком генетичної підгрупи з випадками гомозиготного носійства алелі Т. У групі дітей із Іванківського району з більш високим рівнем гомоцистеїну у крови порівняно з групою дітей із Поліського району реєструвався прямий кореляційний зв'язок між вмістом у крови гомоцистеїну і тиреотропного гормону гіпофіза, гомоцистеїну та трийодтироніну. Можна обґрунтовано припускати негативний вплив пожеж у Чорнобильській зоні відчуження на процеси функціонування фолатного циклу дитячого організму.

Текст научной работы на тему «The state of folate metabolism and its link with thyroid system in children after forest fires in the Chornobyl exclusion zone»



УДК 616.441 -053.2-001.28- https://doi.org/10.32402/dovkil2019.02.010

06:614.84(253):577.164.17:546.15:612.433.441.018

СТАН ФОЛАТНОГО ЦИКЛУ ТА ЙОГО ЗВ'ЯЗОК З ТИРЕО1ДНОЮ СИСТЕМОЮ У Д1ТЕЙ П1СЛЯ Л1СОВИХ ПОЖЕЖ У ЧОРНОБИЛЬСЬК1Й ЗОН1 В1ДЧУЖЕННЯ

Бандажевський Ю.1., Дубова Н.Ф.

THE STATE OF FOLATE METABOLISM AND ITS LINK WITH THYROID SYSTEM IN CHILDREN AFTER FOREST FIRES IN THE CHORNOBYL EXCLUSION ZONE

1BANDAZHEVSKYI Yu.I., 2DUBOVA N.F.

1Ecology and Health Coordination Analytical Centre,

Ivankiv

2National PL. Shupyk Medical Academy of Postgraduate Education, Kyiv

Keywords: folate metabolism, homocysteine, hormones of hypophysis and thyroid gland, forest fires, Chornobyl exclusion zone.

olate cycle (FC) is one of the main metabolic cycles in the human organinsm, folic acid derivatives are involved in its enzyme systems. Moreover, the biosynthesis of methionine, purine and pyrimi-dine nucleotides, and DNA methylation takes place [1]. Homocysteine (Hc) is a sulphur-containing amino acid which is a marker for the efficiency of FM functioning.

Blood Hc levels have exceeded physiological limits in more than 75.0% of the adolescents living in Ivankivskyi and Poliskyi districts, Kyiv region, in 30 years after the accident at the Chornobyl nuclear power plant (ChNPP) [2]. Disorders in the production of thyroid hormones have also been registered [3].

Taking into account a high prevalence of thyroid cancer among the inhabitants of the Ukrainian-Belarusian Polissia after accident at the Chornobyl nuclear power plant [4], a determination of the FC state and its linkwith the thyroid system in children, constantly living under

radiation risk due to the ChNPP accident, is of high priority.

The forest fires at the territory contaminated with radionuclides may be one of the causes of radiation exposure. In total, 4.0 millions hectares of the forest lands were contaminated with radioactive elements in Ukraine. Zhytomyr region (974.3 thousands hectares), Kyiv region (416.4 thousands hectares), Chernihiv region (725.5 thousands hectares), and Rivne region (728.8 thousands hectares) are the most suffered regions [5]. The greatest amount of radioactive fall-out, in particular 137Cs - 4.4 PBq, 9°Sr -4.0 PBq, 239/24opu - 32 TBq, fell within 30-km Chornobyl exclusion zone [6].

Thus, the soils of suffered areas, the forest trees, shrubs, and grasses, growing in these areas, currently contain a huge amount of radioactive elements.

Forest fires, often occurring in the Chornobyl exclusion zone, are one of the most powerful sources of secondary air pollu-

СТАН ФОЛАТНОГО ЦИКЛУ ТА ЙОГО ЗВ ЯЗОК З ТИРЕО1ДНОЮ СИСТЕМОЮ У Д1ТЕЙ П1СЛЯ Л1СОВИХ ПОЖЕЖ У ЧОРНОБИЛЬСЬЮЙ ЗОН1 В1ДЧУЖЕННЯ

1 Бандажевський Ю.1., 2Дубова Н.Ф.

1Координацйний анал'тичний центр "Еколопя \здоров'я", м. 1ванюв, Укра1на 2Нац'юнальна медична академ'(я пслядипломно1 освти iм. П.Л. Шупика, м. Ки1в, Украша

Мета дослщження: визначення стану фолатно-гю циклу та його зв'язку з тиреодною системою у дтей укранського Полсся псля лсових пожеж у Чорнобильсьюй зон вдчуження. Методи дослщження. Iмунюхiмiчний, матема-тико-статистичний.

Результати. У пiдгрупi д'тей-нос'ив алел'1 ризику Т генетичного пюлiмюрфiзму MTHFR:С677Т, як проживають в 1ванювському i Полському районах, рiвень гомоцистену у крови був досто-врно вищим, нж у пiдгрупi дтей, позбавлених дано1 алел'1.

Обстеження дтей 'з район'(в, прилеглих до Чорнобильсько1 атомно1 електростанцп, дозво-

лило виявити у них змiни метабюлiчних прюцесiв у вигляд пщвищено)' продукцп гомоцистену у зв 'язку з лсовими пожежами у зон вдчуження. У групi дтей з lванкiвськюгю району, обстежених псля пожеж\ у Чорнобильсьюй зон в 'щчуження, рiвень гомоцистену у крови вищий, нж у групi дтей Iз Пюлiськюгю району, обстежених до поже-ж, у тому числ'1 у бльшост генетичних пдгруп, за винятком генетично'1 пдгрупи з випадками гомозиготного носйства алел'1 Т. У груп '1 дтей з lванкiвськюгю району з бльш високим рiвнем гомоцистену у крови пюрiвняню з групою дтей з Полського району реестрував-ся прямий кореляцйний зв 'язок мж вмстом у крови гомоцистену \ тиреотропного гормону гiпюфiза, гомоцистену та трийодтиронну. Можна обфунтовано припускати негативний вплив пожеж у Чорнобильсьюй зон вдчуження на процеси функц 'юнування фолатного циклу дитячого орган'зму.

Ключов! слова: фолатний цикл, гомоцисте/н, гормони г!поф!за / щитоподбно/ залози, л!сов! пожеж!, Чорнобильська зона в'щчуження.

© Бандажевський Ю. I., Дубова Н. Ф. СТАТТЯ, 2019.

tion with different radionuclides which have a negative impact on people's health [7].

Radioactive products of combustion of the forest plants move into the atmosphere with wind currents for long distances. The duration of the existence of radiation smoke aerosols and clouds is less than a week in the lower troposphere (the height up to 1.5 km), about a month - in the upper troposphere, and 1-3 years - in the stratosphere. At the same time, radioactive products of combustion are deposited on the radiation-free territories. Basically, radioactive aerosols contain 137Cs [7].

The aim of this study was to determine a state of FC and its link with a thyroid system in the children of the Ukrainian Polissia after forest fires in the Chornobyl exclusion zone.

Material and methods. The study was conducted within the implementation of the projects of the European Commission in Ukraine "Health and Ecological Programmes around the Chor-nobyl Exclusion Zone: Development, Training, and Coordination of Health-Related Projects" and the Rhane-Alpes Regional Council (France).

178 children from Ivankivskyi district and 158 children from Poliskyi district of Kyiv region, underwent laboratory and instrumental examination. According to the findings of dosimetry certification of the settlements, the territory of the regions has remained contaminated with radioactive substances after the Chornobyl accident until the present day (the 137Cs soil pollution density varies 0.171.9 Cu/km2 [8]).

The average age of the children in the group from Ivankivskyi district was (13.6 ± 0.1) years old (95% CI 13.4-13.8 years old), and (14.8 ± 0.0) years old (95% CI 14.7-15.0 years old) in the group from Poliskyi district.

In the morning, all the children who attended school were taken the blood sampling in an empty stomach from the ulnar vein. Blood sampling among children from Poliskyi district was carried out on 02.04.2015 and in the children from Ivankivskyi district - on 18.12.2015.

The investigatons of blood samples were agreed with the

parents, they were analysed at the laboratory, certified by quality standards. A content of pituitary thyroid-stimulating hormone (TSH), free triiodothyronine (T3), free thyroxine (T4), Hc, and the state of the FM genetic system were assessed.

TSH, T3 and T4 concentrations were determined with the help of electrochemiluminescent immu-noassay method (ECLIA). Analyser and test kit: Cobas 6000; Roche Diagnostics (Switzerland).

Plasma homocysteine concentrations were measured with the chemiluminescent immunoassay method (CLIA). Analyser and test kit: Architect 1000 (ABBOT Diagnostics (USA)).

The following allelic variants were identified in genetic analysis of FM: C677T and A1298C of the MTHFR gene (synthesis of the methylenetetrahydrofolate reductase enzyme), A2756G of the MTR gene (synthesis of the B12-dependent methionine syn-thase enzyme) and A66G of the MTRR gene (synthesis of the methionine synthase reductase enzyme). PCR method in a realtime regime was used. Analyser and test kit: DT-96 detecting thermocycler, DNA-Technology (Russia).

In order to carry out the correlation studies identifying a link between blood Hc levels and the frequency of genetic changes in the studied cases of each genetic polymorphism, we assessed genetic variants in points (0-3): "0" - homozygous carriership of a neutral allele; "1" - heterozygous carriership of a risk allele; "2" - homozygous carriership of a risk allele.

The statistical processing of the obtained results was performed with help of IBM SPSS Statistics 22 software (USA). The arithmetic mean (M), ± standard

nPOB^EMM HOPHOBM^fl =

error of mean (m), confidence interval for the mean value (95% CI), median (Me), interquartile range (IR), minimum and maximum parameter values and per-centiles were calculated for the analysed variables. The distribution hypothesis was tested (Kolmogorov-Smirnov criterion). All the parameters under study did not conform to the normal distribution law, thus, a non-parametric Mann-Whitney U-test was used to compare values. The statistical significance of variables was assessed by the determination of p significance level with the help of the statistical software programme.

The Student t-test was used to compare relative values. The critical level of significance for the null hypothesis (p) was taken as 0.05. An link between Hc, TSH, T3 and T4 levels in blood and variants of the carriership of risk alleles of folate metabolism genetic polymorphisms were identified with the help of the Spearman rank correlation coefficient (rxy). The strength of a link was assessed according to a typical scale: weak - from 0 to 0.299; moderate - from 0.3 to 0.699; strong - from 0.7 to 1.0.

Results and discussion. The investigations showed that blood Hc level was significantly higher in the subgroup of the children-carriers of the T risk allele of the MTHFR:C677T genetic poly-morphism-MTHFR:677 C/T + MTHFR:677 genotypes,, living in Ivankivskyi and Poliskyi districts of Kyiv region, than in the subgroup of the children without this allele - MTHFR:677 C/C genotype (tables 1-3).

Hc level was statistically significantly higher in the subgroup with the MTHFR:677 C/T + MTHFR:677 T/T genotypes in comparison with the subgroup that included the MTR:2756 A/G + MTR:2756 G/G genotypes in

THE STATE OF FOLATE METABOLISM AND ITS LINK WITH THE THYROID SYSTEM IN CHILDREN AFTER FOREST FIRES IN THE CHORNOBYL EXCLUSION ZONE 1Bandazhevskyi Yu. I.,2Dubova N. F.

1 Ecology and Health Coordination Analytical Centre, Ivankiv, Ukraine

2National P.L. Shupyk Medical Academy of Postgraduate Education, Kyiv, Ukraine Objective. We determined the state of folate cycle and its link with thyroid system in the children of the Ukrainian Polissia after forest fires in the Chornobyl exclusion zone. Methods: Immunochemical, mathematical and statistical ones.

Results. Blood homocysteine levels were statistically significantly higher in the subgroup of the children who were the carriers of the T risk allele of the MTHFR:C677Tgenetic polymorphism living in Ivankovsky and Poliskyi districts than in the subgroup of the children without this allele. The examination of the children from the regions adjacent to the Chornobyl nuclear power plant allowed to identify in

them the metabolic processes' changes in the form of increased production of Hc due to the forest fires in the exclusion zone. Blood Hc levels were higher in the children from Ivankivskyi district examined after fires in the Chornobyl exclusion zone than in those from Poliskyi district examined before fires, including the majority of genetic subgroups, with the exception of the genetic subgroup which included cases of homozygous carriership of the T allele. Direct links between blood homocysteine and pituitary thyroid-stimulating hormone levels, homocysteine and triiodothyronine levels were detected in the group of the children from Ivankivskyi district who had higher blood homocysteine concentrations compared to the group of children from Poliskyi district. Сonclusions. It can be reasonably assumed that fires in the Chornobyl exclusion zone have a negative effect on the functioning of folate metabolism in a child's organism. Keywords: folate metabolism, homocysteine, hormones of hypophysis and thyroid gland, forest fires, Chоrnobyl exclusion zone.

Table 1

Statistical characteristics of blood Hc values of examined children from Poliskyi and Ivankivskyi districts

Genetic subgroups Poliskyi district Ivankivskyi district

Me IR Me IR

MTR:2756 A/A 10.26 8.39-13.56 11.93 9.73-13.76

MTR:2756 A/G + MTR:2756 G/G 9.69 7.91-11.17 11.46 9.58-13.25

MTHFR:1298 A/A 10.14 7.99-13.04 11.53 9.64-14.22

MTHFR:1298 A/C+ MTHFR:1298 C/C 10.23 8.80-13.13 11.75 10.04-13.30

MTHFR:677 C/C 9.44 7.93-11.16 11.36 9.38-12.97

MTHFR:677 C/T + MTHFR:677 T/T 10.91 8.99-14.31 11.82 10.04-14.85

MTHFR:677 C/T 10.24 8.42-13.18 11.61 9.86-13.31

MTHFR:677 T/T 14.47 10.15-22.78 16.59 12.10-26.71

MTRR:66 A/A 9.26 8.03-3.13 10.86 9.19-13.23

MTRR:66 A/G + MTRR:66 G/G 10.26 8.32-13.10 11.79 9.74-13.52

Total group 10.17 8.30-13.10 11.62 9.69-13.39

Table 2

Results of statistically significant differences when comparing blood Hc values of examined children from Poliskyi district

Comparison groups Comparison group size Average rank Mann-Whitney U test value, significance level, p

MTHFR:677 С/T + MTHFR:677 T/T 79 90.16 U = 2278.5; p = 0.003

MTHFR:677 С/С 79 68.84

MTHFR:677 С/T + MTHFR:677 T/T 79 73.48 U = 1621.0;

MTR:2756 A/G + MTR:2756 G/G 54 57.52 p = 0.019

Table 3

Results of statistically significant differences when comparing blood Hc values of examined children from Ivankivskyi district

Comparison groups Comparison group size Average rank Mann-Whitney U test value, significance level p

MTHFR:677 С/T + MTHFR:677 T/T 98 96.67 U = 3217.0; p = 0.040

MTHFR:677 С/С 80 80.71

the group of children from Poliskyi district (tables 1, 2).

There were no statistical differences in Hc levels between the subgroups of the children that included only cases of homozy-gous variants of a neutral allele and subgroups with a risk allele of the MTR:A2756G, MTHFR:A1298C and MTRR:A66G polymorphisms in the groups of childrens from both districts.

Blood Hc level was statistically significantly higher in the children from Ivankivskyi district than in those from Poliskyi district both in the total group and in the majority of genetic subgroups. There were no statistical differences between the above districts only in the MTHFR:677 C/T + MTHFR:677 T/T, MTHFR:677 T/T and MTRR:66 A/A subgroups (tables 1, 4).

No statistical differences were found in the proportions of risk alleles and neutral alleles of folate metabolism genetic polymorphisms when comparing the groups of children from Poliskyi and Ivankivskyi districts (tables 5, 6).

A weak direct link was found between Hc values and degree of the manifestation of the carrier-ship of the risk allele of the MTHFR:C677T and MTRR:A66G polymorphisms in the groups of children from Poliskyi and Ivankivskyi districts (tables 8, 9).

There were no statistical differences in the frequency of cases of carriership of the T allele of the MTHFR:C677T polymorphism in the similar genetic subgroups of the children from Ivankivskyi and Poliskyi districts (table 7).

No link was observed between Hc values and a degree of the

manifestation of carriership of the risk allele of the MTR:A2756G and MTHFR:A1298C polymorphisms.

Direct links were detected between blood Hc and TSH levels, and Hc and T3 levels in the group of children from Ivankivskyi district in contrast to the group of the children from Poliskyi district. A direct link was observed between TSH and T3, and an inverse link was found between TSH and T4 in both groups of children, which indicated a TSH participation in the formation of T3 (tables 10, 11).

The obtained findings show that the presence of the T allele of the MTHFR:C677T genetic polymorphism contributes to the increased formation of Hc in the organism of the children living in the areas suffered from the accident at the ChNPP. Maximum Hc levels were reported in the group of the children who were the carriers of a homozygous variant of T allele.

Statistically significant differences between Hc values were found in both groups of the children under study between a subgroup with the 100 percent carriership of T allele and a subgroup without cases of carriership of T allele. However, blood Hc level was higher in the children from Ivankivskyi district than in those from Poliskyi district both in a total group and in the majority of genetic subgroups with the exception of a genetic subgroup which included cases of homozy-gous carriership of T allele.

It should be noted that 84 children from the examined group of Poliskyi district were examined again on 18.12.2015 simultaneously with the children from Ivankivskyi district. In this regard, an increase of Hc level in the blood was found in 78.6% of cases in comparison with the state on 02.04.2015 [9].

There were no statistical differences between blood Hc levels in the children with the MTHFR:677 T/T genotype at the marked differences in the children with the MTHFR:677 C/C genotype in this study as well (table 12) [9].

An increase of Hc level was registered in 78.6% of cases among the children of Poliskyi district at the examinations on 02.04.2015 and 18.12.2015.

Thus, it should be stated that a worse course of Hc metabolism is observed in the children from Ivankivskyi district examined on 18.12.2015 in comparison with those from Poliskyi district examined on 02.04.2015.

In addition, the direct links were reported between the He and TSH, He and T3 levels in the group of children from Ivankivskyi district. Thus, He can cause an increase in the production of TSH, and thereby affect the thyroid gland contributing to proliferative processes in its tissues. The correlative links between TSH and T3, T4 registered in both groups of children indicate that the pituitary

hormone is involved in the metabolism of thyroid hormones.

In addition, in the presence of carriership of the G allele of the MTR:2756 polymorphism, He can be converted to cysteine through cystathionine p-syn-thase, and then to selenocys-teine, which forms the active center of deiodinase 5-DI, which catalyzes the conversion of T4 to T3. Due to this mechanism, He levels are lower in this genetic subgroup than in others. At the same time, increased production of T3 can cause serious cardiac

abnormalities.

The absence of statistical differences in the occurrence of FC

Table 4

Results of statistically significant differences when comparing blood Hc values of examined children from Poliskyi1 and Ivankivskyi2 districts

Genetic subgroups Comparison groups Comparison group size Average rank Mann-Whitney U test value, significance level, p

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MTR:2756 A/A 1 104 94.65 U = 4384.0;

2 106 116.14 p = 0.010

MTR:2756 A/G+ 1 54 50.25 U=1228.5;

MTR:2756 G/G 2 72 73.44 p=0.0001

MTHFR:1298 A/A 1 82 73.93 U=2659.5;

2 89 97.12 p=0.002

MTHFR:1298 A/C+ 1 76 72.19 U=2560.5;

MTHFR:1298 C/C 2 89 92.23 p=0.007

MTHFR:677 C/C 1 79 66.18 U=2068.5;

2 80 93.64 p=0.0001

MTHFR:677 C/T + 1 79 81.53 U=3281.0;

MTHFR:677 T/T 2 80 95.02 p=0.082

MTHFR:677 C/T 1 60 62.45 U=1917.0;

2 83 78.90 p=0.019

MTHFR:677 T/T 1 19 17.05 U=134.0;

2 15 18.07 p=0.768

MTRR:66 A/A 1 32 26.33 U=314.5;

2 27 34.35 p=0.074

MTRR:66 A/G + 1 126 119.97 U=7115.0;

MTRR:66 G/G 2 151 154.88 p=0.0001

Total group 1 158 145.64 U =10450.5; p

2 178 188.79 = 0.0001

Presence of polymorphic alleles of in examined children from

Table 5 folate metabolism genes Poliskyi district

Gene, polymorphism "Neutral" allele Risk allele

Absolute number (n) Percentage, % Absolute number (n) Percentage, %

MTR:A2756G 104 65.8 54 34.2

MTHFR:A1298C 82 51.9 76 48.1

MTHFR:C677T 79 50.0 79 50.0

MTRR:A66G 32 20.3 126 79.7

related to forest and peat fires in the Chornobyl exclusion zone in an area of 10.127 ha during the period 26-27.04.2015 and 2829.04.2015 [10] and in an area of 130 ha during the period from 29.06.2015 to 05.07.2015 [11]. In spring and summer of 2015, Table 6

Presence of polymorphic alleles of folate metabolism genes in examined children from Ivankivskyi district

genetic variants among examined groups allows to suggest that an increase in Hc concentrations in the body of children may be associated with the effect of an environmental factor during the period between the two examinations. This factor is

Gene, polymorphism "Neutral" allele Risk allele

Absolute number (n) Percentage, % ' Absolute number (n) Percentage, %

MTR:A2756G 106 59.6 72 40.4

MTHFR:A1298C 89 50.0 89 50.0

MTHFR:C677T 80 44.9 98 55.1

MTRR:A66G 27 15.2 151 84.8

Table 7

Proportion of cases of carriership of T allele of MTHFR:C677T polymorphism in genetic subgroups of children from Ivankivskyi and Poliskyi districts

Genotype Number of cases of carriership of T allele of MTHFR:C677T polymorphism in groups of children

Ivankivskyi district Poliskyi district

Absolute number % Absolute number %

MTR:2756 A/A 61 57.55 50 48.08

MTR:2756 A/G + MTR:2756 G/G 37 50.69 29 53.70

MTHFR:1298 A/A 60 66.67 54 65.85

MTHFR: 1298 A/C + MTHFR:1298 C/C 38 42.70 25 32.90

C/C MTHFR:677 0 0 0 0

MTHFR:677 C/T + MTHFR:677 T/T 98 100 79 100

MTRR:66 A/A 14 51.85 14 43.75

MTRR:66 A/G + MTRR:66 G/G 84 55.26 65 51.59

Table 8

Results of correlation analysis between Hc values and variants of genotypes of folate metabolism polymorphisms in a total group of children from Poliskyi district

Parameter Correlation Parameter

coefficient 1 2 3 4

Spearman's -0.109 0.040 0.283** 0.170*

Hc Sign. (2-tailed), p 0.174 0.615 0.0001 0.033

N 158 158 158 158

Table 9

Results of correlation analysis between Hc values and variants of genotypes of folate metabolism polymorphisms in a total group of children from Ivankivskyi district

Parameter Correlation Parameter

coefficient 1 2 3 4

Spearman's -0.108 -0.026 0.201** 0.177*

Hc Sign. (2-tailed), p 0.151 0.728 0.007 0.018

N 178 178 178 178

Note Table 8-9: * - correlation is significant at the 0.05 level (2-tailed); ** - correlation is significant at the 0.01 level (2-tailed); 1 - MTR:A2756G; 2 - MTHFR:A 1298C; 3 - MTHFR:C677T; 4 - MTRR:A66G.

air currents containing products of combustion of wood, peat, and grass, including radioactive elements spread over long distances from fire sites and affected the population of Ivankivskyi and Poliskyi districts of Kyiv region.

In particular, the 137Cs concentration amounted to 2.5x10-3 Bq/m3 in an air sample taken directly in the fire area on the outskirts of the Poliskyi settlment, which substantially exceeded the reference level established by the exposure standards "Basic reference, clearance and action levels with regard to the radioactive contamination of the facilities of the zone of exclusion and zone of unconditional (obligatory) resettlement" [11].

It is known that inhalation of combustion products, as well as smoking, induces the formation of Hc in the organism [1, 12].

Taking into account the calculations of the collective radiation dose of the critical group of the population, the contingent residing at the territories contaminated with radionuclides in Kyiv, Zhytomyr, and Chernihiv regions have the highest risk of cancer due to the forest fires [5].

Thus, a deterioration of Hc metabolic processes in the children from Ivankivskyi district in comparison with those from Poliskyi district is not associated with homozygous carriership of the T allele of the MTHFR:C677T polymorphism. One can reasonably suggest that there is a connection between fires in the Chornobyl exclusion zone and abnormal functioning of FM in a child's organism resulting in increased blood levels of Hc.

The impact of the forest fires in the Chornobyl exclusion zone as an environmental factor on the developing organism contributes to hyperhomocysteinemia and identification of direct link between Hc and TSH, Hc and T3.

Conclusions

1. Blood Hc level were statistically significantly higher in the subgroup of the children who were the carriers of T risk allele of the MTHFR:C677T genetic polymorphism, living in Ivankivskyi and Poliskyi districts of Kyiv region, than in the subgroup of the children without this allele.

2. The examination of the children from the regions adjacent to

the Chornobyl nuclear power plant allowed to identify changes in metabolic processes among them as the increased production of Нс due to the forest fires in the exclusion zone.

3. Blood Hc levels were higher in the children from Ivankivskyi district examined after the fires in the Chornobyl exclusion zone than in those from Poliskyi district examined before fires, including the majority of genetic subgroups, with the exception of the genetic subgroup which included cases of homozygous carriership of T allele.

4. Direct links were detected between blood Нс and TSH levels, and Нс and Т3 levels in the group of the children from Ivankivskyi district who had higher blood Нс concentrations in comparison with the group of the children from Poliskyi district.

5. It can be reasonably assumed that fires in the Chornobyl exclusion zone have a negative effect on the functioning of folate metabolism in a child's organism.

Л1ТЕРАТУРА

1. Кох Н.В., Слепухина А.А., Лифшиц Г.И. Фолатный цикл: обзор и практические рекомендации по интерпретации генетических тестов. Медицинская генетика. 2015. № 11. С. 3-8.

2. Бандажевский Ю.И., Дубовая Н.Ф. Генетические дефекты при нарушении функционирования цикла фолие-вой кислоты у детей, проживающих на территории, пострадавшей от аварии на ЧАЭС. Зб. наук. праць сп1вроб. НМАПО iM. П.Л. Шупика. К., 2016. Вип. 25. С. 93-98.

3. Бандажевский Ю.И., Дубовая Н.Ф. Лабораторный скрининг в диагностике состояний щитовидной железы у детей из радиоактивно загрязненных районов спустя 30 лет после аварии на Чернобыльской атомной электростанции. Зб. наук. праць cniBpo6. НМАПО iM. П.Л. Шупика. К., 2016. Вип. 26. С. 494-499.

4. Кадун О.Н. Стан здоров'я населения 1ванювського району КиТвськоТ области яке постраждало вщ наслщюв ава-рп на Чорнобильсьюй атомшй електростанцп. Чорнобиль: екологя i здоров 'я: наук. -практ. зб. / за заг. ред. проф. Ю.1. Бандажевського. 1ванюв -Дшпро, 2014. Вип. 1. С. 8-21.

Table 10

Links between metabolic variables in a total group of children from Poliskyi district

Parameter Correlation coefficient Parameter

Нс TSH Т3 Т4

Нс Spearman's 1.000 -0.002 0.130 0.0001

Sign. (2-tailed), p 0.984 0.102 0.998

N 158 158 158 158

TSH Spearman's -0.002 1.000 0.211** -0.239**

Sign. (2-tailed), p 0.984 0.008 0.002

N 158 158 158 158

Тз Spearman's 0.130 0.211** 1.000 0.024

Sign. (2-tailed), p 0.102 0.008 0.760

N 158 158 158 158

Т4 Spearman's 0.0001 -0.239** 0.024 1.000

Sign. (2-tailed), p 0.998 0.002 0.760

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N 158 158 158 158

Table 11 Links between metabolic variables in a total group of children from Ivankivskyi district

Parameter Correlation coefficient Parameter

Нс TSH Т3 Т4

Нс Spearman's 1.000 0.206** 0.157* 0.095

Sign. (2-tailed), p 0.006 0.037 0.207

N 178 178 178 178

TSH Spearman's 0.206** 1.000 0.236** -0.149*

Sign. (2-tailed), p 0.006 0.001 0.047

N 178 178 178 178

Т3 Spearman's 0.157* 0.236** 1.000 -0.010

Sign. (2-tailed), p 0.037 0.001 0.890

N 178 178 178 178

Т4 Spearman's 0.095 -0.149* -0.010 1.000

Sign. (2-tailed), p 0.207 0.047 0.890

N 178 178 178 178

Note Table 10-11: * - correlation is significant at the 0.05 level (2-tailed); ** - correlation is significant at the 0.01 level (2-tailed).

Table 12

Statistical assessment of homocysteine levels in subgroups of examined children from Poliskyi district (n = 84)

Genotype Number of cases Hyperhomocysteinemia Blood Нс levels, pmol/L

Measurement I Measurement II Measurement I Measurement II

Abs. % Abs. % Me IR Me IR

С/С MTHFR:677 44 20 45.5 31 70.51 9.7 7.7-11.1 11.4 9.7-14.12

T/T MTHFR:677 11 9 81.8 11 100 14.5 10.2-19.0 15.0 13.2-22.13

Note: Measurement I - 02.04.2015; Measurement II - 18.12.2015;

1 - statistical differences between Measurements I and II, p<0.05;

2 - statistical differences between Measurements I and II (Wilcoxon T-test standardized score, Z - 4.773, asymptotic significance (two-tailed), p=0.0001);

3 - statistical differences between Measurements I and II (Wilcoxon T-test standardized score, Z - 1.156, asymptotic significance (two-tailed), p=0.248).

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6. Израэль Ю.А., Вакулов-ский С.М., Ветров В.А. и др. Чернобыль: радиоактивное загрязнение природных сред. Л., 1990. 296 с.

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8. Загальнодозиметрична паспортиза^я та результати ЛВЛ-мошторингу у населених пунктах УкраТни, як зазнали радюактивного забруднення тсля ЧорнобильськоТ катаст-рофи. Данi за 2011 р. Збiрка 14. К, 2012. 99 с.

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