Association of the VNTR 4a/4b genetic polymorphism of the eNOS3 gene with arterial hypertension in workers with chronic fluoride intoxication

Introduction. The multiplicity of the factors of the industrial environment, long-term affecting the body in workers in the aluminum industry due to the peculiarities of the technological production of aluminum is related to a high compilation in the air of electrolysis buildings of multi-component suspensions, the predominant of which are fluorides, which have a systemic effect on homeostasis. The development of arterial hypertension is determined by a complex of hemodynamic, neurohormonal, metabolic, and environmental factors associated with individual risk. Mini-satellite NOS3-VNTR, intron 4 of the gene of endothelial nitric oxide synthase is the most important biological mediator, the contribution of which to the development of cardiovascular pathology is undoubtedly high. Evaluation of the early manifestation of hypertension is of priority importance and associated with the definition of genotypes of predisposition / resistance to its development in metallurgists under the conditions of fluoride intoxication.

Materials and methods. One hundred seventy three metallurgists were examined: 92 cases with a proven diagnosis of chronic fluorine intoxication, 81 person with individual signs of fluorine exposure to the skeleton (comparison group). VNTR4 polymorphism of the eNOS3 gene was analyzed using the PCR method, and their relationship with the development of arterial hypertension against the background of chronic fluoride intoxication was assessed.

Results. The associative relationship of the VNT4 polymorphic locus genotypes with fluoride intoxication and concomitant arterial hypertension in non-ferrous metallurgy workers was studied. The distribution of genotypes corresponded to the law of equilibrium populations. Genotype 4a/4a is associated (χ²=9.4810; OR=3.233; p=0.002076) with the development of fluoride intoxication. Homozygote for allele b (4b/4b) is associated with resistance to the studied pathology (χ²=13.5461; OR=0.291; p=0.000233). The level of individual heterozygosity increases: genotype 4a/4b is significantly associated with the development of arterial hypertension against the background of chronic fluoride intoxication (p<0.05).

Limitations. The study is limited by the number of people examined, it is advisable to increase the sample and population control.

Conclusion. The identified genotypes act as markers of the risk of developing hypertension against the background of fluoride intoxication, which makes it possible to recommend genetic testing when forming risk groups to avoid early labour losses in production.

Compliance with ethical standards. The study was approved by the local Ethics Committee of the Research Institute for Complex Problems of Hygiene and Occupational Diseases” (Protocol of the Meeting N 4, § 2 dated November 18, 2021), and was conducted in accordance with the generally accepted scientific principles of the Declaration of Helsinki of the World Medical Association (2013 edition). All participants gave informed voluntary written consent to participate in the study.

Contribution:
Yadykina T.K. – research design, collection and processing of material, statistical analysis, writing the text, editing;
Kazitskaya A.S. – collection and processing of the material;
Gulyaeva O.N. – collection and processing of the material;
Lusina F.A. – collection and processing of the material;
Panev N.I. – collection and processing of clinical data.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

Dedication. The article is dedicated to the memory of the scientist-geneticist Nikolay Ismailovich Gafarov, PhD (Biology), head of the population genetics laboratory of the Research Institute for Complex Problems of Hygiene and Occupational Diseases, whose ideas inspired the authors to conduct this study.

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

Acknowledgement. The study had no sponsorship.

Received: March 6, 2025 / Accepted: March 26, 2025 / Published: April 30, 2025

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