Genetic and biochemical markers of catecholamine metabolism disintegration in patients with vibration disease

Introduction. At the present stage of the development of occupational medicine, vibration sickness (VS) is considered as a chronic systemic disease, which is based on a violation of neurohumoral regulation and the formation of a persistent maladaptation syndrome. Despite the improvement of preventive measures, VS continues to occupy a leading position in the structure of occupational morbidity, which necessitates the search for new molecular genetic markers of pre nosological changes.

The study aims to research the genetic (polymorphic variants rs4680 and rs4633 of the COMT gene) and biochemical markers of the disintegration of catecholamine metabolism in the framework of maladaptation syndrome in patients with vibration disease.

Materials and methods. In a study conducted under a government contract, we examined 75 men of European descent with vibration disease. The authors identified associations between the polymorphic loci rs4680 and rs4633 of the COMT gene and the concentrations of dopamine and tyrosine hydroxylase in blood serum.

Results. Evaluation of the concentrations of dopamine and the enzyme tyrosine hydroxylase in the blood serum of patients with vibration disease (VD) compared with the control group showed no statistically significant differences (p=0.10, p=0.74).

The serum concentrations of dopamine and tyrosine hydroxylase in carriers of the mutant alleles of polymorphisms rs4680 and rs4633 of the COMT gene also did not differ statistically significantly from those of the owners of the main genotype.

Limitations. The main limitation of the work is the relatively small sample size, especially in the control group, which reduces the statistical power of the study. Evaluation of serum concentrations of dopamine and tyrosine hydroxylase demonstrates a systemic neurohumoral status, but does not allow us to conclude about the local state of dopaminergic structures and the catalytic activity of tyrosine hydroxylase. In addition, the simultaneous design of the study cannot be used to assess the cause-effect relationships and dynamics of depletion of dopaminergic reserves during the progression of vibration disease. Multiple comparisons in subgroups increase the risk of false positive results, which, despite the use of nonparametric statistical methods, requires verification on independent samples.

Conclusion. The preservation of the serum concentration of tyrosine hydroxylase at the level of the values of the comparison group confirms the preservation of the potential of the catecholaminergic system at this stage of the development of vibration disease. At the same time, the loss of associative links between polymorphic variants of the COMT gene and dopamine levels indicates a mismatch of the regulatory mechanism. A comprehensive assessment of molecular genetic and biochemical markers makes it possible to conclude that neurotransmitter metabolism in VD is moving to a new level of hormonal and metabolic regulation.

Ethics. The study was conducted in compliance with the ethical standards of the Helsinki Declaration of the last revision and Order No. 200n of the Ministry of Health of the Russian Federation dated 04/01/2016. Conclusion of the local Ethical Committee of the East-Siberian Institute of Medical and Ecological Research No. 5 dated 03/21/2023 All the subjects signed an informed consent to participate in the study.

Contributions:
Chistova N.P. — collecting material, conducting molecular genetic research, statistical processing of material, writing text;
Bodienkova G.M. — design and concept of research, text editing;
Boklazhenko E.V. — conducting research;
Kudaeva I.V. — conceptualization of research;
Naumova O.V. — conducting molecular genetic research;

All co-authors — approving the final version of the article and ensuring the integrity of all parts of the article.

Declaration on the use of artificial intelligence. The authors confirm that artificial intelligence (AI) tools were not used to write semantic content, create research metadata, or generate graphic materials. AI technologies (ChatGPT) were used exclusively at the stage of post-editing the manuscript: for technical formatting of individual text fragments and stylistic correction. The authors exercised full control over the final text and are solely responsible for the originality, scientific reliability and interpretation of the presented data.

Funding. The study had no funding and was carried out within the Framework of the funds of the state assignment of the Federal State Budgetary Educational Institution of Higher Economics.

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

Received: 23.07.2026 / Accepted: 13.08.2026 / Published: 11.09.2026

1. On the state of sanitary and epidemiological well-being of the population in the Russian Federation in 2024: State report. Moscow: Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing; 2025. https://clck.ru/3VDXx8 (in Russian).

2. Cohen S., Janicki-Deverts D., Miller G.E. Psychological stress and disease. JAMA. 2007; 298(14): 1685–1687. https://doi.org/10.1001/jama.298.14.1685

3. Gutsol L.O., Guzovskaiia E.V., Serebrennikova S.N., Seminskу I.Z. Stress (General adaptation syndrome) lecture. Bajkal'skij medicinskij zhurnal. 2022; 1(1): 70–80. https://doi.org/10.57256/2949-0715-2022-1-70-80 https://elibrary.ru/qniekw (in Russian).

4. Daubner S.C., Le T., Wang S. Tyrosine hydroxylase and regulation of dopamine synthesis. Archives of Biochemistry and Biophysics. 2011; 508(1): 1–12. https://doi.org/10.1016/j.abb.2010.12.017 https://elibrary.ru/oahkvr

5. Costa K.M., Schoenbaum G. Dopamine. Curr Biol. 2022; 32(15): 817–824. https://doi.org/10.1016/j.cub.2022.06.060 https://elibrary.ru/zdpnyt

6. Robinson R.G., Smith S.M., Wolkenberg S.E., Kandebo M., Yao L., Gibson C.R et al. Characterization of Non-Nitrocatechol Pan and Isoform Specific Catechol-O-methyltransferase Inhibitors and Substrates. ACS Chem. Neurosci. 2012; 3(2): 129–40. https://doi.org/10.1021/cn200109w

7. Gerra M.C., Dallabona C., Manfredini M., Giordano R., Capriotti C., González-Villar A. et al. The polymorphism Val158Met in the COMT gene: disrupted dopamine system in fibromyalgia patients? Pain. 2024; 165(12): e184-e89. https://doi.org/10.1097/j.pain.0000000000003313 https://elibrary.ru/bexzst

8. Spasova A.P., Barysheva O.Y., Tikhova G.P. The polymorphism of cathechol-O-methyltransferase gene and pain. Regionarnaya anesteziya i lechenie ostroj boli. 2017; 11(1): 6–12. https://elibrary.ru/xxrptr (in Russian).

9. Saloner R., Cherner M., Sundermann E.E., Watson C.W.-M., Iudicello J.E., Letendre S.L. et al. COMT Val158Met genotype alters the effects of methamphetamine dependence on dopamine and dopamine-related executive function: preliminary findings. Psychiatry Research. 2020; 292: 113269. https://doi.org/10.1016/j.psychres.2020.113269 https://elibrary.ru/rjspex

10. Rukavishnikov V.S., Pankov V.A., Lakhman O.L., Bodienkova G.M., Kolycheva I.V., Kuleshova M.V. et al. Common regularities of forming non-specific pathological mechanisms in organism exposure to physical factors of industrial environment. Byulleten' Vostochno-Sibirskogo nauchnogo centra Sibirskogo otdeleniya Rossijskoj akademii medicinskih nauk. 2001; 2: 79–85. https://elibrary.ru/qcgxyn (in Russian).

11. Yakimova N.L., Lizarev V.A., Pankov A.V., Kuleshova M.V., Katamanova E.V., Rukavishnikov V.S. et al. Neurophysiological and morphological effects in the post-exposure vibration period during experimental modeling. Medicina truda i promyshlennaya ekologiya. 2019; 59(5): 284–290. https://doi.org/10.31089/1026-9428-2019-59-5-284-290 https://elibrary.ru/wlxbbf (in Russian).

12. Yamshchikova A.V., Fleishman A.N., Martynov I.D. Evaluation of autonomic disorders in miners with vibration disease. Gigiena i sanitariya. 2023; 102(7): 664–669. https://doi.org/10.47470/0016-9900-2023-102-7-664-669 https://elibrary.ru/qczrmo (in Russian).

13. Sapin M.R., Miliukov V.E., Dolgov E.N., Bogdanov A.V. Modern concepts of the structure and functions of adrenal. Klinicheskaya i eksperimental'naya morfologiya. 2012; 1: 14–20. https://elibrary.ru/pceahv (in Russian).

14. Mineeva M.F., Karpova L.D. Method of assessing prenosologic states from determination of activity of tyrosinehydroxylase forms in white blood cells: Patent No. 2154277; 2000 (in Russian).

15. Zhu M.Y., Raza M.U., Zhan Y., Fan Y. Norepinephrine upregulates the expression of tyrosine hydroxylase and protects dopaminegic neurons against 6-hydrodopamine toxicity. Neurochem. Int. 2019; 131: 104549. https://doi.org/10.1016/j.neuint.2019.104549

16. Kudaeva I.V., Chistova N.P. Occupational determinacy of metabolic syndrome and its proatherogenic components in individuals with vibration disease. Gigiena i sanitariya. 2025; 104(12): 1694–1699. https://doi.org/10.47470/0016-9900-2025-104-12-1694-1699 https://elibrary.ru/rjmyms (in Russian)

17. Dedov I.I., Troshina E.A., Mazurina N.V., Galieva M.O., Logvinova O.V. The role of neurotransmitters in regulation of energy homeostasis and possibility of drug correction of its disturbances in obesity. Ozhirenie i metabolizm. 2016; 13(1): 9–15. https://elibrary.ru/wdhyyt (in Russian).

18. Gmoshinski I.V., Apryatin S.A., Shipelin V.A., Nikitjuk D.B. Neuromediators and neuropeptides — biomarkers for metabolic disturbances in obesity. Problemy endokrinologii. 2018; 64(4): 258–269. https://doi.org/10.14341/probl9466 https://elibrary.ru/ylicuh (in Russian).

19. Romantsova T.I. Reproduction and energy balance: the integrative role of prolactin. Ozhirenie i metabolism. 2014; 11(1): 5–18. https://doi.org/10.14341/OMET201415-18 https://elibrary.ru/sfbfaf (in Russian)

20. Khanh D.V., Choi Y.-H., Moh S.H., Kinyua A.W., Kim K.W. Leptin and insulin signaling in dopaminergic neurons: relationship between energy balance and reward system. Front. Psychol. 2014; 5: 846. https://doi.org/10.3389/fpsyg.2014.00846

21. Kvetňanský, R., Rusnák M., Gašperíková D., Jeloková J., Zórad Š., Vietor I. et al. Hyperinsulinemia and Sympathoadrenal System Activity in the Rat. Annals of the New York Academy of Sciences. 1997; 827: 118–134. https://doi.org/10.1111/j.1749-6632.1997.tb51827.x

22. Fiory F., Perruolo G., Cimmino I., Cabaro S., Pignalosa F.C., Miele C. et al. The Relevance of Insulin Action in the Dopaminergic System. Front. Neurosci. 2019; 13: 868. https://doi.org/10.3389/fnins.2019.00868 https://elibrary.ru/mkhhct

23. Kullmann S., Blum D., Jaghutriz B.A., Gassenmaier C., Bender B., Häring H.-U. et al. Central Insulin Modulates Dopamine Signaling in the Human Striatum. The Journal of Clinical Endocrinology & Metabolism. 2021; 106(10): 2949–2961. https://doi.org/10.1210/clinem/dgab410 https://elibrary.ru/ejofpg

24. Mychka V.B., Chazova I.E. Metabolic syndrome. Sistemnye gipertenzii. 2009; 1: 50–53. https://elibrary.ru/mwfbvd (in Russian)

25. Figlewicz D.P., Bennett J.L., Aliakbari S., Zavosh A., Sipols A.J. Insulin acts at different CNS sites to decrease acute sucrose intake and sucrose self-administration in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2008; 295(2): R388–94. https://doi.org/10.1152/ajpregu.90334.2008