Prognostic role of the 4a/4b genetic polymorphism of the locus VNTR-NOS3 intron 4 in the development of respiratory pathology in metallurgists with chronic occupational intoxication with fluoride compounds

Introduction. The multiplicity of environmental factors affecting the body of workers in the aluminum industry is combined with the nature of the influence of multicomponent finely dispersed suspensions detected in the air of electrolysis enclosures, the predominant among which are fluorides, which have a systemic effect on the functional state of the body. The development of bronchopulmonary pathology is determined by a complex of systemic, metabolic, and hemodynamic disorders associated with individual risk. The polymorphism of the endothelial nitric oxide synthase (eNOS3) gene makes a significant contribution to the differentiation of respiratory disorders against the background of chronic intoxication, which determines the need to study the associative links of eNOS3 with the development of comorbid respiratory pathology in metallurgists.

The study aims to research the prognostic relationship of polymorphism 4a/4b of the VNTR4 locus of the eNOS3 gene in metallurgists with the development of respiratory pathology occurring against the background of chronic fluoride intoxication.

Materials and methods. The scientists conducted a survey of 85 aluminum production workers with chronic fluoride intoxication combined with respiratory tract diseases and a comparison group of 61 people without an established diagnosis.

The PCR method was used to perform a genetic analysis of the VNTR4 polymorphism of the eNOS3 gene and to determine its prognostic value in the development of respiratory dysfunction.

Results. Non-ferrous metallurgy workers have an associative association of the VNTR4-eNOS3 locus with concomitant bronchopulmonary pathology on the background of chronic fluoride intoxication. The distribution of the studied genotypes corresponded to the law of population equilibrium. It was shown that genotype 4a/4a is associated (χ²=5.4498; OR=2.4654; p=0.0195) with the development of combined respiratory pathologies and 4a/4b VNTR (χ²=7.1681; OR=4.4231; p=0.0081) with the risk of developing chronic dust bronchitis.

Limitations. The study is limited to the number of people with long, continuous work experience in the conditions of aluminum electrolysis, who have not retired from production, and who are being examined at the clinic of the KPGPZ Research Institute. It is advisable to expand the sample within the professional cohort under study and analyze haplotypes, as well as their relationship to functional indicators.

Conclusion. The identified genotypes act as markers of the risk of developing respiratory pathology against the background of chronic intoxication with fluoride and its compounds, which makes it possible to recommend genetic screening when forming risk groups in order to avoid early industrial labor losses.

Ethics. The study was approved by the Ethics Committee of the Research Institute of Complex Problems of Hygiene and Occupational Diseases (Minutes of meeting No. 4, § 2 dated 11/18/2021), conducted in accordance with the generally accepted scientific principles of the Helsinki Declaration of the World Medical Association (ed. 2013).

Contributions:
Yadykina T.K. — research design, collection and processing of biological material, statistical analysis, writing, editing;
Panev N.I. — collection and processing of clinical data;
Kazitskaya A.S. — collection and processing of material;
Ulanova E.V. — material processing;
Gulyaeva O.N. — analysis of literature and genetic data;
Semenova E.A. — collection and analysis of clinical data.

Funding. The study had no funding.

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

Received: 19.09.2025 / Accepted: 11.11.2025 / Published: 10.12.202

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