Biomarkers of stress in children with asthenic syndrome associated with aluminum contamination in biological media and A/G polymorphism of the HTR2A (rs7997012) serotonin receptor gene

Introduction. Ambient air pollution with heavy metals, included aluminum, creates their elevated levels in children and leads to rather early decompensation of weak genetically heritable systems of the body including the nervous system.

Materials and methods. We examined eighty six 4–7 years children with asthenic syndrome. Fifty two of them (the test group) lived and attended preschool facilities in a zone influenced by emissions from aluminum production (a dose created by a non-ferrous metallurgic plant is 5.65×10^–5 mg/(kg·day)). The reference group was made of 34 children who lived on a conditionally clean territory and were exposed to airborne aluminum in a dose of 3.0×10^–6 mg/(kg·day). Within this study, there were examined several children’s biological media including urine (aluminum), blood (serotonin and cortisol), and buccal epithelium (HTR2A rs7997012 gene). Differences were considered to be significant at a p<0.05.

Results. We established statistically significantly higher aluminum levels in urine (1.3 times higher) in the test group against the reference one (0.012±0.0001 and 0.0092±0.0012 respectively); authentically higher prevalence of the minor allele G of the HTR2A (rs7997012) serotonin receptor gene (authentically 1.6 times higher in the test group against the reference one). Both these factors create an elevated risk of asthenic syndrome, 1.86 times higher in the test group (OR=1.86; 95%CI (1.02–3.67)) together with lower serotonin levels (130.28±32.42 ng/ml and 183.35±34.57 ng/ml respectively) and higher cortisol levels (278.08±25.90 nmol/cm3 and 191.28±21.62 nmol/cm³ respectively).

Limitations. The limitation is application of the identified stress biomarkers for diagnostics of nervous system disorders that manifest themselves in children through asthenic syndrome associated with exposure to aluminum.

Conclusion. A/G replacement of the HTR2A (rs7997012) gene creates a 1.86 times higher risk of asthenic syndrome (OR=1.86; 95%CI (1.02–3.67)) for children with elevated aluminum levels in urine under inhalation exposure to it in a dose equal to 5.65×10^–5 mg/kg·day). The disease would have such a peculiarity as longer recurrence and its biomarkers include an imbalance between indicators of a developing stress, cortisol, and serotonin.

Compliance with ethical standards. The study was accomplished in compliance with the WMA Declaration of Helsinki (revised in 2013) and approved by the local ethics committee of the Federal Scientific Center of Medical and Preventive Health Risk Management Technologies of the Federal Service for Surveillance over Consumer Rights Protection and Human Wellbeing – Protocol No. 5 of June 03, 2022.

Consent. Each participant (or their legal representative) gave an informed voluntary consent to take part in the study and to their personal medical data being published in impersonal form in the Hygiene and Sanitation journal

Contributions:
Dolgikh О.V. — study design and concept, editing the text;
Zaitseva N.V. — study design and concept, editing the text;
Subbotina А.А. — data collection and analysis, statistical analysis, writing the text;
Kazakova О.А. — data collection and analysis, statistical analysis, writing the text;
Alikina I.N. — data collection and analysis, statistical analysis, writing the text.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

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

Acknowledgement. The study had no sponsorship.

Received: August 28, 2023 / Accepted: September 26, 2023 / Published: November 20, 2023