Assessment of the effect of the CNTF gene rs1800169 polymorphism on serum dopamine levels in patients with vibration disease

Introduction. The modern stage in the study of vibration disease (VD) is characterized by a significant expansion of research in the field of investigating the role of neurotrophic factors that ensure the viability of the neuron and the functioning of the nervous system, as well as the identification of candidate genes encoding the processes underlying the development and course of the disease. An important regulator of brain dopamine neurons is ciliary neurotrophic factor (CNTF), which not only protects neurons from damage but regulates their functions. The functional significance of endogenous CNTF and the polymorphism of its genes to regulate the dopaminergic system are still not well understood.

Materials and methods. Serum dopamine concentrations were determined by ELISA. Genotyping of the rs1800169 CNTF gene polymorphism was performed by real-time PCR.

Results. In VD patients, an increase in the serum concentration of dopamine and autoantibodies to dopaminergic receptors has been established, which may indicate to changes in the corresponding neuronal systems. The distribution of genotype carriers for the rs1800169 CNTF gene polymorphism in VD individuals was: GG — 72 (0.81); AG — 15 (0.17); AA — 2 (0.02), and alleles — A — 2 (0.02); G — 159 (0.89) and corresponded to the Hardy-Weinberg equilibrium. Positive correlation relationship between frequency of detection of mutant allele A and dopamine level was revealed. The relative risk of exposure of carriers of the AG genotype of the rs1800169 polymorphic locus of the CNTF gene to the group of VD patients and dopamine levels above the reference values is 5.7 times more common than GG carriers.

Limitations. The limitations of this work are due to small groups of employees.

Conclusion. The association of the rs1800169 polymorphic locus of the CNTF gene with the serum dopamine concentration in VD patients was revealed. Mutant allele A is associated with an elevation in endogenous dopamine levels. Defective secretion of intracellular CNTF in the central nervous system appears to lead to increased dopamine production.

Compliance with ethical standards. All procedures performed in studies involving human participants were in accordance with the ethical standards the 2013 Helsinki declaration and Order No. 200n of the Ministry of Health of the Russian Federation of 01.04.2016 “On Approval of Good Clinical Practice Rules”.

Contribution:
Bodienkova G.M. — concept and design of research, collection and processing of material, writing of text;
Boklagenko E.V. — collection and processing of material, statistical processing;
Chistova N.P. — collection and processing of material, statistical processing.
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 the absence of obvious and potential conflicts of interest in connection with the publication of this article.

Acknowledgment. The work was performed within the framework of funds allocated for the implementation of the state task East-Siberian Institute of Medical and Ecological Research.

Received: April 2, 2024 / Revised: May 17, 2024 / Accepted: June April 9, 2024 / Published: July 17, 2024