Associations of the variable site rs2010963 of the VEGF-A gene with multifocal atherosclerosis in aluminum industry workers with chronic occupational intoxication with fluoride compounds

Introduction. The aluminum industry occupies a leading position among non-ferrous metallurgy industries in revealing somatic pathologies in workers that occur against the background of chronic fluoride intoxication. Long-term exposure to fluorides on the body has a cardiovasotoxic effect, leads to structural and functional disorders of the myocardium and the development of comorbid cardiovascular pathology. This dictates the need for a risk-oriented approach to its diagnosis, including one based on molecular genetic analysis, for the timely identification of risk groups for the development of atherosclerosis and the elaboration of preventive measures aimed at preserving the health and maintaining working longevity of the studied occupational cohort.

Materials and methods. There were examined ninety seven metallurgists with a previously proven diagnosis of chronic occupational intoxication with fluoride compounds, engaged in aluminum production. The comparison group consisted of 33 workers of this enterprise without a proven occupational disease. All respondents underwent ultrasound investigation of the main arteries. Genotyping of the rs2010963 polymorphic locus of the VEGF-A gene was carried out in a 96-well format using TaqMan technology (allele-specific real-time PCR).

Results. The associative connection of the G/G VEGF-A genotype is determined in metallurgists with the risk of developing chronic occupational intoxication with fluoride compounds and heterozygous G/C genotype in subjects with multifocal atherosclerosis. The high level of predictive value of the polymorphism -634 G/C (rs2010963) of the VEGF-A gene allows considering it a marker of the risk for the developing atherosclerosis in workers exposed to long-term impact to fluoride compounds on the body.

Limitations. The study was limited to the number of long-term work experienced subjects undergoing periodic medical examinations and undergoing inpatient treatment at the Research Institute for Complex Problems of Hygiene and Occupational Diseases.

Conclusion. It is recommended to conduct a screening molecular and genetic analysis in a clinical hospital setting for timely assessment of the prognostic significance of risk markers for the development of atherosclerosis and its complications in workers of basic occupations engaged in aluminum production.

Compliance with ethical standards. All subjects signed an informed consent to participate in a study that meets the requirements of the Bioethical Committee of the Research Institute for Complex Problems of Hygiene and Occupational Diseases, executed in accordance with the Declaration of Helsinki of the World Medical Association “Ethical Principles for Medical Research Involving Human Subjects” as amended 2013 and the “Rules of Proper Clinical Practice” approved by Order of the Ministry of Health of the Russian Federation dated April 1, 2016 Nо. 200n.

Contribution:
Yadykina T.K. — the concept and design of the study, collection and processing of material, conducting molecular and genetic studies, statistical analysis, writing text;
Korotenko O.Yu. — ultrasound diagnostics, literature analysis;
Kazitskaya A.S. — collection of material, conducting molecular and genetic studies;
Semenova E.A. — collection of clinical material;
Zhukova A.G. — the concept and design of the study, editing.
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: December 15, 2023 / Revised: January 15, 2024 / Accepted: April 9, 2024 / Published: May 8, 2024