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8
УДК 616-053.2-001.28-008.9:612.015.31:546. 41:546.18-06:614.73:621.039.004.6
https://doi.org/10.32402/ dovkil2019.04.051
ЗАЛЕЖН1СТЬ МЕТАБОЛ1ЧНИК АСОЦ1АЦ1Й КАЛЬЦ1Ю I ФОСФОРУ В1Д СТАНУ ГЕНОМА ФОЛАТНОГО ЦИКЛУ У Д1ТЕЙ, ЯК1 ПРОЖИВАЮТЬ НА ТЕРИТОР11, ЩО ПОСТРАЖДАЛА В1Д АВАРИ
НА ЧОРНОБИЛЬСЬК1Й АТОМН1Й ЕЛЕКТРОСТАНЦП
Бандажевський Ю.1., Дубова Н.Ф.
THE METABOLIC RELATIONSHIP OF CALCIUM AND PHOSPHORUS TO THE STATE OF GENOME OF FOLATE METABOLISM IN CHILDREN LIVING IN THE AREAS SUFFERED FROM THE CHORNOBYL NUCLEAR POWER PLANT ACCIDENT
1 BANDAZHEVSKYI Yu.I., 2DUBOVA N.F.
1Ecology and Health Coordination and Analytical Centre, Ivankiv, Ukraine 2P.L. Shupyk National Medical Academy of Postgraduate Education, Ministry of Health of Ukraine, Kyiv, Ukraine
Keywords: folate metabolism, genotype, homocysteine, calcium, phosphorus, hormones, radioactive contaminated territory.
xploring the mechanisms of mineral metabolism regulation is of great importance in the organisation of curative and preventive measures of osteoporosis - a disease that leads to bone fractures [1].
Despite the wide prevalence of osteoporosis, its pathogenesis is poorly studied. A relationship has been found between the risk of osteoporosis in adults and elevated blood levels of homocysteine - a metabolite of the essential amino acid methionine [2].
It has been concluded that homocysteine is a predictor of bone fractures in adults [3]. Nearly 30 years after the accident at the Chornobyl nuclear power plant (CNPP), hyperho-mocysteinemia has been reported in a large number of the chil-
dren examined living under conditions of constant radiation exposure [4]. In this regard, it is important to determine a relationship of calcium and phosphorus with hormones regulating mineral metabolism taking into account the state of genome of folate metabolism affecting homocysteine formation.
The purpose of this study was to identify associations between blood levels of calcium, phosphorus and hormones regulating mineral metabolism, taking into account the state of genome of folate metabolism in children living in a district affected by the Chornobyl accident.
Material and methods. The study was conducted within the implementation of projects of the European Commission in Ukraine
ЗАЛЕЖНСТЬ МЕТАБОЛ1ЧНИХАСОЦ1АЦ1Й КАЛЬЦЮI ФОСФОРУ В1Д СТАНУ ГЕНОМА ФОЛАТНОГО ЦИКЛУ У Д1ТЕЙ, ЯК1 ПРОЖИВАЮТЬ НА ТЕРИТОР11, ЩО ПОСТРАЖДАЛА В1Д АВАРЙ НА ЧОРНОБИЛЬСЬКЙ АТОМНЙ ЕЛЕКТРОСТАНЦП'
1 Бандажевський Ю.1., 2Дубова Н.Ф.
1 Координашйний аналтичний центр «Еколопя i здоров 'я», м. 1ванюв, Укра'на 2Нац'юнальная медична академ'(я пслядипломноï освти iM. П.Л. Шупика, м. Ки'в, Укра'на
Мета дослдження: визначення кореляцйних зв 'язюв мiж вмстом у крови кальцю, фосфору i гормонами, що регулюють мнеральний обмн, з урахуванням стану генома фолатного циклу у дтей, як проживають у район '!, що постраждав вд аварй на Чорнобильськй атомнй електростанци. Методи дослдження: 'мунох'ш'чний, матема-тико-статистичний.
Результати. При обстеженн дтей, якi меш-кають у район'1, що постраждав вд авари на Чорнобильськй атомнй електростанцп, найбль-шу питому вагу випадкв ппергомоцистешеми було виявлено у групах з генотипами T/T MTHFR:677 i G/G MTR:2756. Удтей, якi проживають у район '1, що постраждав в 'щ аварй' на ЧАЕС, Р пор!вняно з Са, мае бльш т'1сн'1 зв'язки з гормонами, якi регулюють мнеральний обмн. У дтей, якi проживають в умовах пос^йного рад'а-
цйного впливу, носйство генотипу Т/Т MTHFR:677, що супроводжуеться вираженою ппергомоцисте)'нем'ею, сприяе формуванню зворотного кореляшйного зв'язку середньо)' сили мiж Са i ТТГ. Водночас в ус\х генетичних групах фолатного циклу в 'щсутш кореляцiйнi зв'язки м'ж Са i ПТГ, Са i Р. У групах 100% носй-ства алелей ризику полiморфiзмiв MTHFR:C677T i MTR:A2756G зв'язок м'ж Р i ПТГбув в'щсутн'м. У групах з гомозиготним носйством зазначених алелей ризику (генотипи T/T MTHFR:677 i G/G MTR:2756) не виявлено зв'язюв Р з гормонами, що регулюють мнеральний обмiн. Зниження активност ферменлв метлентетрапдрофолат-редуктази i В12-залежно1 мет'юн'н-синтази, у зв'язку з носйством алелей ризику генетичних полiморфiзмiв MTHFR:С677Т i MTR:A2756G, при-зводить до порушення фiзiологiчноï регуляци фосфорного обмну. Ошнку стану кальцй-фос-форного обмну у дтей 'з район'1в, що постраж-дали в 'щ авари на ЧАЕС, сл 'щ проводити з ураху-ванням р'вня гомоцистену у крови i генотипу фолатного циклу. Отриманi результати можуть бути використаними п '1д час розробки програми профлактики порушень мiнерального обмну у дтей, як проживають у районах, що постражда-ли в д авари на ЧАЕС.
Ключовi слова: фолатний цикл, генотип, гомоцисте)'н, кальц'ш, фосфор, гормони, рад'юактивно забруднена територ 'ш.
© Бандажевський Ю.1., Дубова Н. Ф. СТАТТЯ, 2019.
51 Environment & Health № 4 2019
«Health and Ecological Programmes around the Chornobyl Exclusion Zone: Development, Training and Coordination of Health-Related Projects» and the Rh$ne-Alpes Regional Council (France). 158 children (78 boys and 80 girls) from Polessky district of Kiev region underwent laboratory examination. According to data of dosimetry certification of settlements, the territory of the district has remained contaminated with radioactive substances after the CNPP accident until the present day (having the 137Cs soil contamination density of 0.17 up to 1.9 Cu/km2) [5].
The examined children's average age was (14.8±0.1 ) years old (95% CI 14.7-15.0 years old).
All the children who attended school had blood drawn from the ulnar vein after fasting in the morning.
The blood samples were analysed at a laboratory certified under quality standards with the agreement of the parents. Thus, we assessed blood levels of homocysteine (Hc), ionized calcium (Ca), phosphorus (P), para-
thyroid hormone (PTH), calcitonin (CT), pituitary thyroid-stimulating hormone (TSH), free triiodothyronine (T3), free thyroxine (T4), Cortisol (C) and the state of the genetic system of folate metabolism (FM).
Plasma homocysteine concentrations were measured using a chemiluminescent immunoassay (CLIA) method. Analyser and test kit: Architect 1000 (ABBOT Diagnostics, USA). Plasma homocysteine levels in the children of over 10 pmol/L were defined as hyperhomocysteinemia.
Ca levels were measured using an ion-selective method. Analyser and test kit: AVL 9180; Roche Diagnostics (Switzerland). The reference values were 1.161.32 mmol/L.
P concentrations were determined using the spectrophotometry method. Analyser and test kit: Cobas 6000, Roche Diagnostics (Switzerland). The reference values for boys were 0.95-1.65 mmol/L, for girls -0.90-1.55 mmol/L.
PTH concentrations were determined using an electrochemilumi-
Table 1
Groups of children with a certain FM polymorphism genotype
Group number Genotype Group number Genotype
1 MTR:2756 A/A 7 MTHFR:677 C/C
2 MTR:2756 A/G 8 MTHFR:677 C/T
3 MTR:2756 G/G 9 MTHFR:677 T/T
4 MTHFR:1298 A/A 10 MTRR:66 A/A
5 MTHFR:1298 A/C 11 MTRR:66 A/G
6 MTHFR:1298 C/C 12 MTRR:66 G/G
Proportion of hyperhomocysteinemia in groups of examined children
Group number Genotype Number of children in a group Number of cases with Hc>10 Mmol/L
Absolute number %
1 MTR:2756 A/A 104 58 55.8
2 MTR:2756 A/G 45 18 40.0
3 MTR:2756 G/G 9 8 88.9
4 MTHFR:1298 A/A 82 42 51.2
5 MTHFR:1298 A/C 60 33 55.0
6 MTHFR:1298 C/C 16 9 56.3
7 MTHFR:677 C/C 79 34 43.0
8 MTHFR:677 C/T 60 35 58.3
9 MTHFR:677 T/T 19 15 79.0
10 MTRR:66 A/A 32 12 37.5
11 MTRR:66 A/G 72 37 51.4
12 MTRR:66 G/G 54 35 64.8
General group 158 84 53.2
nescent immunoassay (ECLIA) method. Analyser and test kit: Cobas 6000; Roche Diagnostics (Switzerland). The reference values were 15.0-65.0 pg/mL.
T3 concentrations were measured using an electrochemilumi-nescent immunoassay (ECLIA) method. Analyser and test kit: Cobas 6000; Roche Diagnostics (Switzerland). The reference values were 2.3-5.0 pg/mL.
T4 levels were determined using an electrochemilumines-cent immunoassay (ECLIA) method. Analyser and test kit: Cobas 6000; Roche Diagnostics (Switzerland). The reference values were 1.1-1.8 ng/dL.
TSH concentrations were determined using an electrochemilumi-nescent immunoassay (ECLIA) method. Analyser and test kit: Cobas 6000; Roche Diagnostics (Switzerland). The reference values were 0.27-4.2 uIU/mL.
CT levels were measured using a chemiluminescent immunoassay (CLIA) method. Analyser and test kit: Immulite (Siemens AG), Germany. The reference values were up to 11.5 pg/mL.
C levels were measured using an electrochemiluminescent im-munoassay (ECLIA) method. Analyser and test kit: Cobas 6000; Roche Diagnostics (Switzerland). The reference values were 6.2-19.4 Mg/dL.
The following allelic variants were identified during genetic analysis of FM: C677T and A1298C of the MTHFR gene (synthesis of the methylenete-trahydrofolate reductase enzyme), A2756G of the MTR gene (synthesis of the B12-dependent methionine synthase enzyme) and A66G of the MTRR gene (synthesis of the methionine synthase reductase enzyme). A realtime PCR method was used. Analyser and test kit: DT-96 detecting thermocycler, DNA-Technology (Russia).
During the study, we formed groups of children with a certain genotype of the FM polymorphisms under study (table 1).
The statistical processing of the results obtained was performed using the IBM SPSS Statistics 22 software (USA). The arithmetic mean (M), ± standard error of mean (m), confidence interval for the mean value (95% CI), median (Me), interquartile range (IR), minimum and maximum parameter values and per-
Table 2
centiles were calculated for the variables analysed. The distribution hypothesis was tested (a Kolmogorov-Smirnov test). 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 determining a significance level for p with the help of the statistical software programme.
The Student's t-test was used to compare relative values. The critical level of significance for the null hypothesis (p) was set at 0.05. Associations between levels of Hc and Ca, He and P, as well as Ca and P and PTH, CT, TSH, T3, T4, and C were identified with the help of Spearman's rank correlation coefficient (rxy). The strength of the association was assessed according to a typical scale: weak - 0 to 0.299; moderate - 0.3 to 0.699; strong - 0.7 to 1.0.
Results and discussion. The proportion of hyperhomo-cysteinemia in separate genetic groups reflected the state of FM. This value had statistical differences with the same value in most groups, except for the groups № 3, 5, 8, 12, and in the group № 3 in most groups, except the group № 9 (tables 2, 3).
During the study, the following associations of ionized Ca were found:
a) a weak inverse association with T4 in the group 5, carriership of the MTHFR:1298 A/C genotype;
b) a moderate inverse association with T4 in the group 10, carriership of the MTRR:66 A/A genotype;
c) a weak direct association with CT in the group 8, carrier-ship of the MTHFR:677 C/T genotype;
d) a moderate inverse association with TSH in the group 9, carriership of the MTHFR:677 T/T genotype (table 4).
During the study, the following associations of P were observed:
Direct associations with PTH (moderate), with TSH and T3 (weak); an inverse association with T4 (weak); in the group 1 (carriership of the MTR:2756 A/A genotype);
A direct association with T3 (moderate), an inverse associa-
nPOB^EMM HOPHOBM^fl =
Direct associations with TSH and T3 (weak), and an inverse association with T4 (moderate) in the group 8 (carriership of the MTHFR:677 C/T genotype);
Direct associations with PTH and T3 (moderate) in the group 10 (carriership of the MTRR:66 A/A genotype);
Direct associations with PTH and T3 (weak) in the group 11 (carriership of the MTRR:66 A/G genotype);
Direct associations with PTH and TSH (weak), inverse associations with C (moderate), with T4 (weak) in the group 12 (carriership of the MTRR:66 G/G genotype) (table 5).
Thus, during the study we found associations between Ca
Table 3
Results of statistically significant differences when comparing blood Hc levels in the children examined
tion with C (moderate) in the group 2 (carriership of the MTR:2756 A/G genotype);
Direct associations with T3 (moderate), with PTH (weak) in the group 4 (carriership of the MTHFR: 1298 A/A genotype);
A direct association with PTH (weak) in the group 5 (carriership of the MTHFR:1298 A/C genotype);
A direct association with PTH (moderate) in the group 6 (carri-ership of the MTHFR:1298 C/C genotype);
Direct associations with PTH and T3 (moderate), with TSH (weak) in the group 7 (carriership of the MTHFR:677 C/C genotype);
Comparison groups Statistical significance Comparison groups Statistical significance
1 t=2.88 1 t=4.81
9 p=0.005 3 p=0.000010
2 t=4.02 2 t=5.57
9 p=0.0004 3 p=0.000011
3 t=1.23 4 t=3.26
9 p=0.23 3 p=0,0021
4 t=2.26 5 t=2.93
9 p=0.028 3 p=0.006
5 t=1.59 6 t=4.05
9 p=0.06 3 p=0.001
6 t=2.50 7 t=6.18
9 p=0.02 3 p=0.00001
7 t=4.23 8 t=2.64
9 p=0.0001 3 p=0.0012
8 t=1.68 9 t=1.23
9 p=0.099 3 p=0.23
10 t=3.87 10 t=5.2
9 p=0.0007 3 p=0.00007
11 t=3.17 11 t=4.9
9 p=0.0026 3 p=0.00002
12 t=1.63 12 t=3.15
9 p=0.109 3 p=0.003
and hormones involved in mineral metabolism in certain genetic groups of children from the raions affected by the CNPP accident. An inverse association between Ca and TSH in the group
9 with the MTHFR:677 T/T genotype was the most pronounced (table 4). The greatest number of cases of hyperhomocysteinemia (tables 2, 3) and the highest blood levels of homocysteine were found in this group [6].
The heterozygous version of carriership of the T allele of this polymorphism - group 8 -MTHFR:677 C/T genotype - was accompanied by a smaller proportion of cases of hyperhomo-cysteinemia and lower blood levels of Hc, moreover, there was no association between Ca and TSH, as well as in the case of absence of carriership of the T allele - group 7 - MTHFR:677 C/C genotype.
Thus, the formation of an inverse association between Ca and TSH occurred in the groups of carriership of the MTHFR:677 T/T genotype in the presence of the largest proportion of cases of hyperhomocysteinemia and the highest blood Hc levels.
The studies conducted showed a moderate inverse association between Ca and T4 in the group
10 - MTRR:66 A/A genotype, and a weak inverse association between Ca and T4 in the group 5 - MTHFR: 1298 A/C genotype,
as well as a weak association between Са and CT in the group 8 - MTHFR:677 С/T genotype (table 4).
No associations were found between Ca and PTH, Ca and P in all the genetic groups of FM of the cohort of children examined.
P had more associations than Ca (table 5). First of all, these are moderate direct associations between P and PTH in the groups of carriers of homozygous variants of neutral polymorphisms: group 1 - MTR:2756 A/A, group 7 - MTHFR:677 С/С, group 10 -MTRR:66 A/A, as well as associations between Р and Т3 in the following groups: 1 - MTR:2756 A/A, 4 - MTHFR:1298 A/A, 7 -MTHFR:677 С/С, 10 - MTRR:66 A/A.
A moderate direct association was observed between Р and TSH in the group 12 - MTRR:66 G/G. A moderate association was reported with cortisol in the same group and in the group 2 -MTR:2756 A/G. A moderate inverse association was detected between Р and Т4 in the group 8 -MTHFR:677 С/T, and weak inverse associations were found between Р and Т4 in the groups 1 - MTR:2756 A/A and 12 -MTRR:66 G/G.
Thus, it should be noted that there is a presence of associations between Р and PTH, Р and Т3 in the groups formed on the basis of 100% carriership of
Table 4
Associations between Ca and hormones values in groups of children with different genetic polymorphisms
Group № Parameter Correlation coefficient Parameters
Т4, ng/dL CT, pg/mL TSH, ulU/mL
5 Ca, mmol/L Spearman's -0.2761
Sign. (2-tailed), p 0.033
N 60
8 Ca, mmol/L Spearman's 0.2551
Sign. (2-tailed), p 0.049
N 60
9 Ca, mmol/L Spearman's -0.6382
Sign. (2-tailed), p 0.003
N 19
10 Ca, mmol/L Spearman's -0.3591
Sign. (2-tailed), p 0.044
N 32
Notes: 1 - correlation is significant at the 0.05 level (2-tailed); 2 - correlation is significant at the 0.01 level (2-tailed).
homozygous variants of neutral alleles of FM polymorphisms. No associations were observed between P and hormones regulating mineral metabolism in the group 9 - MTHFR:677 T/T and in the group 3 - MTR:2756 G/G.
In our opinion, this may be due to a larger proportion of cases of hyperhomocysteinemia in these groups (tables 2, 3). The association between Р and PTH disappears and the one between Р and Т3 weakens significantly already in the presence of heterozygous carriership of risk alleles in the groups 8 (MTHFR:677 С/Т genotype) and 2 (MTR:2756 A/G genotype) (table 5).
Given that Нс contributes to the development of osteoporosis [2], its increased production in the group of children - carriers of the MTHFR:677 T/T genotype may be regarded as an event that contributes to bone demineral-ization and the release of Са into the blood.
At the same time, folic acid status should be taken into account. The homozygous car-riership of the T allele of the MTHFR:C677T polymorphism was accompanied by the lowest blood levels of folic acid [7, 8] in the groups of children from the districts affected by the CNPP accident.
The negative effect of the Т/Т MTHFR:C677T genotype and low levels of folic acid, as well as riboflavin in the blood on bone mineralization in adults is known [9].
It also should be noted that the MTR:2756 G/G genotype has a negative effect on mineral metabolism, since there is a blocking of transfer of the methyl group to Hc, because of the lack of activity of the B12-dependent methionine synthase enzyme.
Thus, there are no associations between P and hormones involved in mineral metabolism, in particular PTH and Т3 in the groups of children who are carriers of the MTHFR:677 Т/Т and MTR:2756 G/G genotypes.
The findings show that the genome of FM plays an important role for the physiological regulation of calcium/phosphorus metabolism in the body of children living under conditions of environmental distress associated with the accident at the CNPP.
In light of this, it is necessary to take into account the state of genome of folate metabolism and blood homocysteine concentrations when organising medical preventive activities against osteoporosis in children living in districts affected by the CNPP accident.
Conclusions
The largest proportion of cases of hyperhomocysteinemia was found in the groups with the MTHFR:677 T/T and MTR:2756 G/G genotypes when examining the children living in the districts affected by the CNPP accident.
In the children living in the district affected by the CNPP accident, P has stronger associations with hormones that regulate mineral metabolism compared to Ca.
In the children living under constant radiation exposure, the car-riership of the MTHFR:677 T/T genotype accompanied by marked hyperhomocysteinemia contributes to the formation of the moderate inverse association between Ca and TSH. At the same time, no associations were found between Ca and PTH, Ca and P in all genetic groups of folate metabolism.
There was no association between P and PTH in the groups with 100% carriership of the risk alleles of the MTHFR:C677T and MTR:A2756G polymorphisms.
No associations were observed between P and hormones that regulate mineral metabolism in the groups with homozygous carriership of the above risk alle-les (MTHFR:677 T/T and MTR:2756 G/G genotypes).
The decrease in the activity of the methylenetetrahydrofolate reductase and B12-dependent methionine synthase enzymes due to the carriership of risk alle-les of the MTHFR:C677T and MTR:A2756G genetic polymorphisms leads to impaired physiological regulation of phosphorus metabolism.
The assessment of calcium/phosphorus metabolism in children from districts affected by the CNPP accident should be carried out taking into account blood homocysteine levels and folate metabolism genotype.
The findings can be used in developing a programme for the prevention of mineral metabolism diseases in children living in areas affected by the CNPP accident.
.niTEPATyPA
1. Clarke M., Ward M., Strain J.J. et al. B-vitamins and bone in health and disease: the current evidence. Proc. Nutr. Soc. 2014. № 73. P. 330-339.
2. Ravichandran S., Ashish K.J., Krishnagopal R., Surendher K.R. Serum homocysteine levels and the risk of Osteoporosis. Int. J. Med.
Res. Rev. 2016. Vol. 4. № 4. P. 557-561.
3. McLean R.R., Jacques P.F., Selhub J. et al. Homocysteine as a predictive factor for hip fracture in older persons. Engl. J. Med. 2004. Vol. 350. № 20.
P. 2042-2049.
4. Бандажевский Ю.И., Дубовая Н.Ф. Гипергомоцистеине-мия и В12-фолиевый дефицит
Table 5
Associations between the values of P and hormones in groups of children with different genetic polymorphisms
Group № Parameter Correlation coefficient Parameters
PTH, pg/mL TSH, ulU/mL Т3, pg/mL Т4, ng/dL C, Mg/dL
1 Р, mmol/L Spearman's 0.4822 0.2011 0.2592 -0.2161
Sign. (2-tailed), p 0.0001 0.041 0.008 0.028
N 104 104 104 104
2 Р, mmol/L Spearman's 0.3031 -0.3101
Sign. (2-tailed), p 0.043 0.038
N 45 45
4 Р, mmol/L Spearman's 0.2801 0.3972
Sign. (2-tailed), p 0.011 0.0001
N 82 82
5 Р, mmol/L Spearman's 0.2831
Sign. (2-tailed), p 0.029
N 60
6 Р, mmol/L Spearman's 0.5191
Sign. (2-tailed), p 0.039
N 16
7 Р, mmol/L Spearman's 0.4112 0.2241 0.3262
Sign. (2-tailed), p 0.0001 0.047 0.003
N 79 79 79
8 Р, mmol/L Spearman's 0.2841 0.2931 -0.3762
Sign. (2-tailed), p 0.028 0.023 0.003
N 60 60 60
10 Р, mmol/L Spearman's 0.4051 0.4812
Sign. (2-tailed), p 0.021 0.005
N 32 32
11 Р, mmol/L Spearman's 0.2601 0.2721
Sign. (2-tailed), p 0.027 0.021
N 72 72
12 Р, mmol/L Spearman's 0.2701 0.3261 -0.2701 -0.3281
Sign. (2-tailed), p 0.049 0.016 0.049 0.016
N 54 54 54 54
«
Notes: 1 - correlation is significant at the 0.05 level (2-tailed); 2 - correlation is significant at the 0.01 level (2-tailed).
THE METABOLIC RELATIONSHIP OF CALCIUM AND PHOSPHORUS TO THE STATE OF GENOME OF FOLATE METABOLISM IN CHILDREN LIVING IN THE AREAS SUFFERED FROM THE CHORNOBYL NUCLEAR POWER PLANT ACCIDENT 1 Bandazhevskyi Yu.I., 2Dubova N.F.
1 Ecology and Health Coordination and Analytical Centre, Ivankiv, Ukraine 2National P.L. Shupyk Medical Academy of Postgraduate Education, Ministry of Public Health of Ukraine, Kyiv
A state of hyperhomocysteinemia was revealed in the large number of examined children living under conditions of constant radiation exposure. At the same time, taking into account the connection of homocys-teine with the processes of osteogenesis, it is important to show the connection of calcium and phosphorus with hormones that regulate mineral metabolism, including the state of the folate cycle genome. Objective: We identified the correlations between blood levels of calcium, phosphorus, and hormones regulating mineral metabolism, taking into account the state of genome of folate metabolism in children living in a district suffered from the accident at the Chornobyl nuclear power plant. Methods: We used immunochemical and mathe-matical-and-statistical methods. Results: When examining children living in the area suffered from the accident at the Chornobyl nuclear power plant, the largest proportion of cases of hyperhomocysteinemia was found in the groups with T/T MTHFR: 677 and G/G MTR: 2756 genotypes. In children living in the area suffered from the accident
at the ChNPP, P, in comparison with Ca, has closer links with hormones that regulate mineral metabolism. In children living under conditions of constant radiation exposure, the bearing of T/T MTHFR: 677genotype, accompanying by the severe hyperhomocysteinemia, contributes to the formation of the inverse correlation of the medium force between Ca and TSH. At the same time, there are no correlations between Ca and PTH, Ca and P in all genetic groups of the folate cycle. There was no connection between P and PTH in the groups of 100% bearing of risk alleles of MTHFR: C677T and MTR: A2756G polymorphisms. There were no connections of P with hormones that regulate mineral metabolism in the groups with homozygous bearing of noted risk alleles (genotypes T/T MTHFR: 677 and G/G MTR: 2756). A decrease in the activity of methylenete-trahydrofolate reductase and B12-dependent methionine synthase enzymes, in connection with the bearing of risk alleles of MTHFR: C677T and MTR: A2756G genetic polymorphisms, leads to impaired physiological regulation of phosphoric metabolism. Assessment of calcium-phosphorus metabolism in children from the areas suffered from the accident at the Chornobyl NPP should be carried out taking into account the level of homocysteine in blood and the genotype of folate cycle. The obtained results can be used in the development of the program on the prevention of mineral metabolism disorders in children living in the areas suffered from the accident at the ChNPP.
Keywords: folate metabolism, genotype, homocysteine, calcium, phosphorus, hormones, radioactive contaminated territory.
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