Genetic profile in children with musculoskeletal pathology under conditions of airborne exposure to heavy metals

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Introduction. Diseases of the musculoskeletal system develop largely due to environmental pollution, especially with heavy metals. Lead, manganese, and nickel are the most common and toxic pollutants that affect on the immature bone, immune, and nervous systems in children.

Materials and methods. We examined homeostasis and the genetic profile of one hundred eight 7–11 years schoolchildren with dorsopathy from an industrially developed region. The observation group was made of children with dorsalgia (class M54.9). Polymorphic variants of candidate genes, dopamine receptor DRD2 (rs1800497) and the main histocompatibility complex HLA-DRA C/T (rs3135388), were identified by real-time PCR.

Results. The average daily dose of exposure to airborne nickel (6.39 µg/(kg · day)), manganese (15.3 µg/(kg · day)), and lead (0.6 µg/(kg · day)) was 35.5, 43.7 and 11.8 times higher in the observation area against the reference one. Schoolchildren with dorsopathy, combined with dorsalgia, had levels of manganese, nickel and lead in blood 1.3, 1.43, and 2 times higher respectively than the reference range. At the same time, the children from the observation group showed increased frequency of the variant T-allele of the DRD2 gene (rs1800497) (OR=3.76; CI: 1.53–9.28, relative risk: RR=1.73; CI: 1.33–2.22; p<0.005) and the C-allele of the HLA-DRA C/T gene (rs3135388) (OR=4.40; CI: 1.30–14.95) associated with excessive levels of dopamine and ionized calcium.

Limitations of the study are related to the need to increase the sample and verify the obtained results.

Conclusion. Established average daily doses of exposure to airborne nickel, manganese and lead (6.39 µg/(kg · day), 15.3 µg/(kg · day) and 0.6 µg/(kg · day)) were 35.5, 43.7 and 11.8 times respectively higher for the observation group against the reference one. The study reported features of polymorphism of candidate genes DRD2 (rs1800497) and HLA-DRA C/T (rs3135388) in children with dorsopathy complicated by dorsalgia syndrome, associated with disorders of neuroimmune controlling and bone density. They cause additional risk (RR=1.73; CI:1.33–2.22) of pathology of the musculoskeletal system in case biological media are contaminated with lead, manganese, and nickel, which modifies the course of dorsopathy by adding dorsalgia.

Compliance with ethical standards. The study was approved by the Ethics committee of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies (Protocol No.7 of March 14, 2023). All participants (or their legal representatives) gave informed voluntary written consent to participate in the study.

Contribution:
Otavina E.A. – data collection and analysis, statistical analysis, writing the text;
Kazakova O.A. – statistical analysis, writing the text.
All authors are responsible for the integrity of all parts of the manuscript and have approved its final version.

Conflict of interest. The authors declare no conflict of interest.

Acknowledgement. The study had no sponsorship.

Received: August 12, 2024 / Revised: August 23, 2024 / Accepted: November 19, 2024 / Published: December 17, 2024

About the authors

Elena A. Otavina

Federal Scientific Center for Medical and Preventive Health Risk Management Technologies

Email: eleninca@mail.ru

Junior Researcher of the Department of Immunobiological Diagnostic Methods of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Perm, 614045, Russian Federation

e-mail: eleninca@mail.ru

Olga A. Kazakova

Federal Scientific Center for Medical and Preventive Health Risk Management Technologies

Author for correspondence.
Email: noemail@neicon.ru

Senior Researcher, Head of the Immunogenetics Laboratory of the Department of Immunobiological Diagnostic Methods of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Perm, 614045, Russian Federation

References

  1. Valina S.L., Shtina I.E., Maklakova O.A., Ustinova O.Yu., Eisfeld D.A. Regularities in diseases of the musculoskeletal system developing in schoolchildren under complex exposure to environmental factors and factors related to lifestyle. Health Risk Analysis. 2021; (3): 54–66. https://doi.org/10.21668/health.risk/2021.3.05.eng https://elibrary.ru/zduumj
  2. Zolotnikova G.P., Kaptsov V.A., Kurguz R.V. Influence of technogenic pollution on health indices of students of lycees. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2017; 96(5): 470–4. https://doi.org/10.18821/0016-9900-2017-96-5-470-474 https://elibrary.ru/ysqdif (in Russian)
  3. Oleynikova T.A., Pozhidaeva D.N., Oreshko A.Yu. Prevalence survey of musculoskeletal and connective tissue disorders in the Russian Federation. Sovremennaya farmakoekonomika i farmakoepidemiologiya. 2019; 12(1): 5–13. https://doi.org/10.17749/2070-4909.2019.12.1.5-13 https://elibrary.ru/cyzxcb (in Russian)
  4. Pokatilov A.B., Nova A.P., Sarvanova S.V., Yaroshenko I.P. Worrisome trends in the incidence of musculoskeletal system in children and adolescents and prospects their prevention. Glavvrach Yuga Rossii. 2020; (1): 19–22. https://elibrary.ru/nptjqu (in Russian)
  5. Mansurova G.Sh., Maltsev S.V., Ryabchikov I.V. Features of formation of the musculoskeletal system in schoolchildren: diseases, causes and possible ways of correction. Prakticheskaya meditsina. 2019; 17(5): 51–5. https://elibrary.ru/kfyxcj (in Russian)
  6. Mansurova G.Sh., Maltsev S.V., Ryabchikov I.V. Estimation of calcium supply of children with musculoskeletal system pathology. Prakticheskaya meditsina. 2018; (2): 52–6. https://elibrary.ru/yxorqw (in Russian)
  7. Akhpolova V.O., Brin V.B. Actual concepts of heavy metals’ kinetics and pathogenesis of toxicit. Vestnik novykh meditsinskikh tekhnologii. 2020; 27(1): 55–61. https://doi.org/10.24411/1609-2163-2020-16578 (in Russian)
  8. Martínez-Martínez M.I., Muñoz-Fambuena I., Cauli O. Neurotransmitters and Behavioral Alterations Induced by Nickel Exposure. Endocr. Metab. Immune. Disord Drug Targets. 2020; 20(7): 985–91. https://doi.org/10.2174/1871530319666191202141209
  9. Budinger D., Barral S., Soo A.K.S., Kurian M.A. The role of manganese dysregulation in neurological disease: emerging evidence. Lancet Neurol. 2021; 20(11): 956–68. https://doi.org/10.1016/S1474-4422(21)00238-6
  10. Mirzoev E.B., Kobyalko V.O., Polyakova I.V., Gubina O.A. Metabolism and mechanisms of cytotoxic action of the lead in mammals. Sel’skokhozyaistvennaya biologiya. 2018; 53(6): 1131–41. https://doi.org/10.15389/agrobiology.2018.6.1131rus https://elibrary.ru/yyfqhb (in Russian)
  11. Chen P., Totten M., Zhang Z., Bucinca H., Erikson K., Santamaría A., et al. Iron and manganese-related CNS toxicity: mechanisms, diagnosis and treatment. Expert Rev. Neurother. 2019; 19(3): 243–60. https://doi.org/10.1080/14737175.2019.1581608
  12. Song X., Fiati Kenston S.S., Kong L., Zhao J. Molecular mechanisms of nickel induced neurotoxicity and chemoprevention. Toxicology. 2017; 392: 47–54. https://doi.org/10.1016/j.tox.2017.10.006
  13. Rondanelli M., Faliva M.A., Peroni G., Infantino V., Gasparri C., Iannello G., et al. Essentiality of manganese for bone health: an overview and update. Natural Product Communications. 2021; 16(5): 1–8. https://doi.org/10.1177/1934578X211016649
  14. Baj J., Flieger W., Barbachowska A., Kowalska B., Flieger M., Forma A., et al. Consequences of disturbing manganese homeostasis. Int. J. Mol. Sci. 2023; 24(19): 14959. https://doi.org/10.3390/ijms241914959
  15. Conley T.E., Richardson C., Pacheco J., Dave N., Jursa T., Guazzetti S., et al. Bone manganese is a sensitive biomarker of ongoing elevated manganese exposure, but does not accumulate across the lifespan. Environ. Res. 2022; 204(Pt. D): 112355. https://doi.org/10.1016/j.envres.2021.112355
  16. Chiang T.I., Lane H.Y., Lin C.H. D2 dopamine receptor gene (DRD2) Taq1A (rs1800497) affects bone density. Sci. Rep. 2020; 10(1): 13236. https://doi.org/10.1038/s41598-020-70262-0
  17. Andersson Svärd A., Benatti E., Lundgren M., Lernmark Å., Maziarz M., Elding Larsson H. Possible relationship between the HLA-DRA1 intron haplotype of three single-nucleotide polymorphisms in intron 1 of the HLA-DRA1 gene and autoantibodies in children at increased genetic risk for autoimmune type 1 diabetes. Immunohorizons. 2022; 6(8): 614–29. https://doi.org/10.4049/immunohorizons.2200039
  18. Sato D., Narita M., Hamada Y., Mori T., Tanaka K., Tamura H., et al. Relief of neuropathic pain by cell-specific manipulation of nucleus accumbens dopamine D1- and D2-receptor-expressing neurons. Mol. Brain. 2022; 15(1): 10. https://doi.org/10.1186/s13041-021-00896-2
  19. Santa Maria M.P., Hill B.D., Kline J. Lead (Pb) neurotoxicology and cognition. Appl. Neuropsychol. Child. 2019; 8(3): 272–93. https://doi.org/10.1080/21622965.2018.1428803
  20. Puopolo M. The hypothalamic-spinal dopaminergic system: a target for pain modulation. Neural. Regen. Res. 2019; 14(6): 925–30. https://doi.org/10.4103/1673-5374.250567
  21. Cha M., Choi S., Kim K., Lee B.H. Manganese-enhanced MRI depicts a reduction in brain responses to nociception upon mTOR inhibition in chronic pain rats. Mol. Brain. 2020; 13(1): 158. https://doi.org/10.1186/s13041-020-00687-1

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2025



СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 37884 от 02.10.2009.