The role of polymorphic loci of cytokine genes in the development of atherosclerosis in miners with dust lung pathology

Introduction. Miners have a high incidence of occupational and industrial-related diseases. Combined pathology of the respiratory and cardiovascular systems is most often observed. Atherosclerosis occupies a central place in cardiovascular diseases, the pathogenesis of which has a complex nature, including inflammatory, autoimmune, neurohumoral, and molecular genetic mechanisms.

The purpose of the study was to evaluate the contribution of polymorphisms of pro- and anti-inflammatory cytokine genes to the formation of atherosclerosis of various location in coal miners with occupational dust lung pathology.

Materials and methods. There were examined one hundred ninety four coal mine workers with long-term labour experience. All cases were divided into 2 groups at stage 1: the main group – 129 miners with a previously proven diagnosis of “dust lung pathology”; the comparison group – 65 miners of the same coal enterprises working in similar conditions, but without occupational disease of the bronchopulmonary system. At the second stage of the study, all patients with dust lung pathology were divided into subgroups matched by sex, age, and ethnicity. The first subgroup included the miners with dust lung pathology burdened with atherosclerosis (n=77), the second group consisted of the persons with dust lung pathology without atherosclerosis (n=52). DNA was isolated from the venous blood of all the examined patients, followed by genotyping using the Real-Time allele-specific polymerase chain reaction.

Results. A statistically significant relationship was found between the presence of dust lung pathology and the formation of atherosclerosis in long-term labour experience miners (χ²=5.02; p=0.026; OR=2.08; 95% CI=1.14–3.82). The contribution of the rs1800795 polymorphism of the IL-6 gene and the rs2243250 one of the IL-4 gene to the formation of occupational dust lung pathology had been detected. The genotypes of risk (homozygote for the T allele of the IL-4 gene and the G/C heterozygote of the IL-6 gene) and resistance (homozygote for the C allele of the IL-4 gene and homozygote for the G allele of the IL-6 gene) were identified. An analysis of the frequency of distribution of the studied genotypes between the miners with dust lung pathology in combination with atherosclerosis and a group of people with occupational pulmonary pathology without atherosclerosis revealed no significant differences.

Limitations. The investigation conducted has limitations in the number of studied genes that contribute to the formation of atherosclerosis. The limitation is the relatively small number of the subjects obtained by dividing the total sample of the patients with dust pathology into subgroups with or without atherosclerosis.

Conclusion. The results obtained may indicate an indirect effect of the rs1800795 polymorphism of the IL-6 gene and the rs2243250 one of the IL-4 gene on the development of atherosclerosis in miners with occupational bronchopulmonary pathology, which proves the need for further study of the pathogenesis of atherosclerosis among coal industry workers with the determination of not only individual genetic markers of predisposition and resistance, but also intergene interactions.

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 No. 3, § 1 of April 08, 2021). The examination of patients was carried out on the basis of ethical standards elaborated 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 N 200n.

Contribution:
Kazitskaya A.S. – the concept and design of the study, collection and processing of material, statistical processing, writing a text;
Yadykina T.K. – processing of material;
Doroshilova A.V. – statistical processing;
Zhukova A.G. – 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: July 27, 202 / Revised: May 25, 2024 / Accepted: June 19, 2024 / Published: July 31, 2024