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

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