Effect of the rs1800795 polymorphism of the IL-6 gene on echocardiographic parameters in miners with occupational dust lung pathology

Introduction. The Kuzbass coal industry is characterized by a high prevalence of occupational and industrial-related diseases. The combined effects of a complex of harmful industrial factors contribute to the formation of associated pathology of the respiratory and cardiovascular systems. The pathogenetic role of inflammation triggered by the cytokine cascade in the initiation of cardiovascular pathology has been proven. The key role in the development of which is given to cytokines with proinflammatory activity, in particular interleukin-6.

Purpose of the investigation was to identify the relationship of the polymorphic locus rs1800795 of the IL-6 gene with echocardiographic parameters in miners with occupational lung dust pathology.

Materials and methods. A total of one hundred fifty miners with long-term labour experience were examined. The main group consisted of 110 miners with a previously proven diagnosis of “dust lung pathology”. Then, all patients with an occupational diagnosis were divided into 3 subgroups depending on the carriage of genotypes of the rs1800795 polymorphism of the IL-6 gene. The comparison group included 40 miners working in similar conditions who do not have a proven occupational disease of the respiratory system. All patients underwent genetic studies: genotyping of single-nucleotide polymorphic loci of the rs1800795 gene of the IL-6 gene by the method of allele-specific polymerase chain reaction in real time. The morphological and functional state of the heart was assessed using echocardiography according to the standard technique on the Vivid E9 ultrasound system manufactured by General Electric.

Results. Carriers of different genotypes of the polymorphic marker C(-174)G of the IL-6 gene had significantly different early filling rate and left ventricular ejection fraction. The minimum values of both echocardiographic parameters were found in the group of miners with dust lung pathology, who were owners of the heterozygous GG genotype of the C(-174)G polymorphic marker of the IL-6 gene. Differences in the structural and functional parameters of the heart were revealed between miners with dust lung pathology with different genotypes of the rs1800795 polymorphism of the IL-6 gene and patients of the comparison group. The holders of all three genotypes showed a significant increase in the average pressure in the pulmonary artery compared with the group of individuals without occupational pathology. The rate of early filling of the left ventricle, its ejection fraction, as well as the ratio of the rate of early and late filling of the left ventricle were maximum in the comparison group, having statistically significant differences with homozygotes for the G-allele among the miners with occupational lung pathology.

Limitations. The study was limited by the number of miners undergoing in-depth periodic medical examination at the Clinic of the Research Institute for Complex Problems of Hygiene and Occupational Diseases.

Conclusion. The results of the study indicate a predisposition of miners with occupational pathology of the bronchopulmonary system, owning the G/G genotype of the rs1800795 polymorphism of the IL-6 gene to the formation of left ventricular dysfunction. Studying the genetic predisposition to the development of structural and functional disorders of the heart among certain occupational groups will allow timely identifying workers with a high risk of chronic heart failure. The revealing initial myocardial changes based on genetic analysis will facilitate timely prevention aimed at reducing the incidence of possible cardiovascular complications against the background of occupational pathology of the respiratory system in coal mine workers.

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 No. 4 dated November 18, 2021) conducted in accordance with the generally accepted scientific principles of the Helsinki Declaration of the World Medical Association as amended 2013. All participants gave informed voluntary written consent to participate in the study.

Contribution:
Kazitskaya A.S. – concept and design of the study, statistical processing, writing the text;
Korotenko O.Yu. – collection of material, editing;
Yadykina T.K. – collection of material and data 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 no conflict of interest.

Acknowledgment. The study had no sponsorship.

Received: January 22, 2025 / Revised: February 24, 2025 /Accepted: March 26, 2025 / Published: April 30, 2025

1. Nechiporenko V.V., Boeva I.A., Tereshchuk B.P. The need for complex research to study the share of the contribution of production factors in the development and current of cardiovascular diseases of workers of the coal industry. Vestnik gigieny i epidemiologii. 2021; 25(2): 188–9. https://elibrary.ru/eunyjc (in Russian)

2. Panev N.I., Korotenko O.Yu., Filimonov E.S., Gostyaeva E.P. Risk factors for the development of arterial hypertension in vibration disease in coal industry workers. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2024; 103(7): 693–9. https://doi.org/10.47470/0016-9900-2024-103-7-693-699 https://elibrary.ru/hewclm (in Russian)

3. Chukaeva I.I., Orlova N.V., Goryainova S.V., SpiryakinaYa.G., Nasedkina T.V., Arkhipova V.S., et al. Study of genetic polymorphisms in patients with cardiovascular disease risk factors. Meditsinskii alfavit. 2018; 1(3): 6–10. https://elibrary.ru/xplehb (in Russian)

4. Aimagambetova A.O., Karazhanova L.K., Kotlyar A., Tokbulatova M.O. Cytokine gene polymorphism with myocardial infarction in subjects of Russian nationality. Nauka i zdravookhranenie. 2016; (5): 121–30. https://elibrary.ru/xaaohz (in Russian)

5. Bautista L.E., Vera L.M., Arenas I.A., Gamarra G. Independent association between inflammatory markers (C-reactive protein, interleukin‐6, and TNF-α) and essential hypertension. J. Hum. Hypertension. 2005; 19(2): 149–54. https://doi.org/10.1038/sj.jhh.1001785

6. Khazova E.V., Boulashova O.V., Valeeva E.V. Study of the rs1800795 polymorphism of the IL6 gene to verify the clinical portrait of a patient with chronic heart failure: gender aspects. Consilium Medicum. 2022; 24(10): 741–6. https://doi.org/10.26442/20751753.2022.10.201757 https://elibrary.ru/oexapu (in Russian)

7. Aimagambetova A.О., Karazhanova L.K., Kotlyar A. Cytokine profile in patients with acute myocardial infarction with and without complications. Klinicheskaya meditsina. 2017; 95(3): 233–7. https://elibrary.ru/yqagsf (in Russian)

8. Riikola A., Sipilä K., Kähönen M., Jula A., Nieminen M.S., Moilanen L., et al. Interleukin-6 promoter polymorphism and cardiovascular risk factors: The Health 2000 Survey. Atherosclerosis. 2009; 207(2): 466–70. https://doi.org/10.1016/j.atherosclerosis.2009.06.004

9. Rai H., Colleran R., Cassese S., Joner M., Kastrati A., Byrne R.A. Association of interleukin 6 -174 G/C polymorphism with coronary artery disease and circulating IL-6 levels: a systematic review and meta-analysis. Inflamm. Res. 2021; 70(10–12): 1075–87. https://doi.org/10.1007/s00011-021-01505-7

10. Toutouzas K., Klettas D., Anousakis-Vlachochristou N., Melidis K., Azilazian Z., Asimomiti M., еt al. The -174 G>C interleukin-6 gene polymorphism is associated with angiographic progression of coronary artery disease over a 4-year period. Hellenic. J. Cardiol. 2017; 58(1): 80–6. https://doi.org/10.1016/j.hjc.2017.02.002

11. Hou H., Wang C., Sun F., Zhao L., Dun A., Sun Z. Association of interleukin-6 gene polymorphism with coronary artery disease: an updated systematic review and cumulative meta-analysis. Inflamm. Res. 2015; 64(9): 707–20. https://doi.org/10.1007/s00011-015-0850-9

12. Zheng G.H., Chen H.Y., Xiong S.Q. Polymorphisms of -174G>C and -572G>C in the interleukin 6 (IL-6) gene and coronary heart disease risk: a meta-analysis of 27 research studies. PLoS One. 2012; 7(4): e34839. https://doi.org/10.1371/journal.pone.0034839

13. Phulukdaree A., Khan S., Ramkaran P., Govender R., Moodley D., Chuturgoon A.A. The interleukin-6 -147 g/c polymorphism is associated with increased risk of coronary artery disease in young South African Indian men. Metab. Syndr. Relat. Disord. 2013; 11(3): 205–9. https://doi.org/10.1089/met.2012.0130

14. Nikulina S.Yu., Marilovtseva O.V., Chernova A.A., Tretyakova S.S., Nikulin D.A., Maksimov V.N. The role of interleukin-6 gene in development of idiopathic sick sinus syndrome. Rossiiskii kardiologicheskii zhurnal. 2016; 21(10): 32–6. https://doi.org/10.15829/1560-4071-2016-10-32-36 https://elibrary.ru/wyyogj (in Russian)

15. Manginas A., Tsiavou A., Chaidaroglou A., Giamouzis G., Degiannis D., Panagiotakos D., et al. Inflammatory cytokine gene variants in coronary artery disease patients in Greece. Coron. Artery. Dis. 2008; 19(8): 575–82. https://doi.org/10.1097/MCA.0b013e32831286e8

16. Brull D.J., Montgomery H.E., Sanders J., Dhamrait S., Luong L., Rumley A., et al. Interleukin-6 gene -174 G > C and -572 G > C promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery. Arterioscler. Thromb. Vasc. Biol. 2001; 21(9): 1458–63. https://doi.org/10.1161/hq0901.094280.

17. Humphries S.E., Luong L.A., Ogg M.S., Hawe E., Miller G.J. The interleukin-6 -174 G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in healthy men. Eur. Heart J. 2001; 22(24): 2243–52. https://doi.org/10.1053/euhj.2001.2678 https://elibrary.ru/inqjyt

18. Cheng Z., Zhang C., Mi Y. IL-6 gene rs1800795 polymorphism and diabetes mellitus: a comprehensive analysis involving 42,150 participants from a meta-analysis. Diabetol. Metab. Syndr. 2022; 14(1): https://doi.org/10.1186/s13098-022-00851-8 https://elibrary.ru/hxbhda

19. Tiis R.P., Osipova L.P. Interleukin-6: it’s role in the organism, genetic polymorphism and significance in certain diseases (literature review). Meditsinskaya genetika. 2022; 21(1): 14–27. https://doi.org/10.25557/2073-7998.2022.01.14-27 https://elibrary.ru/wvcnmu (in Russian)

20. Minushkina L.O., Chumakova O.S., Selezneva N.D., Evdokimova M.A., Osmolovskaya V.S., Blagodatskikh K.A., et al. Left ventricular hypertrophy development, associated with genetic polymorphism of inflammatory mediators. Rossiiskii kardiologicheskii zhurnal. 2014; 19(10): 23–8. https://elibrary.ru/stdmar (in Russian)

21. Berg K.K., Madsen H.O., Garred P., Wiseth R., Gunnes S., Videm V. The additive contribution from inflammatory genetic markers on the severity of cardiovascular disease. Scand. J. Immunol. 2009; 69(1): 36–42. https://doi.org/10.1111/j.1365-3083.2008.02187.x

22. Jin Y., Wang Q., Wang G., Zhang X., Yan B., Hu W. Common polymorphism in the interleukin-6 gene and myocardial infarction risk: a meta-analysis. Genet. Test. Mol. Biomarkers. 2014; 18(5): 330–40. https://doi.org/10.1089/gtmb.2013.0404 https://elibrary.ru/yelemt

23. González-Castro T.B., Hernández-Díaz Y., Pérez-Hernández N., Tovilla-Zárate C.A., Juárez-Rojop I.E., López-Narvaez M.L., et al. Interleukin 6 (rs1800795) gene polymorphism is associated with cardiovascular diseases: a meta-analysis of 74 studies with 86,229 subjects. EXCLI J. 2019; 18: 331–55. https://doi.org/10.17179/excli2019-1248 https://elibrary.ru/nlgejp

24. Khidirova L.D., Yakhontov D.A., Maximov V.N., Zenin S.A. The association of genotype and alleles 174G/C (rs1800795) frequency of IL6 gene with clinical data in patients with atrial fibrillation in combination with extra-cardiac pathology. Mezhdunarodnyi zhurnal serdtsa i sosudistykh zabolevanii. 2019; 7(21): 12–9. https://elibrary.ru/yradmn (in Russian)

25. Starkova K.G., Dolgikh O.V., Krivtsov A.V., Kazakova O.A., Mazunina A.A. Features of eNOS and HTR2A genetic polymorphism in the implementation of the productioninduced cardiovascular pathology in workers at the underground mining enterprise. Meditsina truda i promyshlennaya ekologiya. 2019; 59(11): 966–9. https://doi.org/10.31089/1026-9428-2019-59-11-966-969 https://elibrary.ru/zvbzes (in Russian)

26. Dolgikh O.V., Starkova K.G., Krivtsov A.V., Bubnova O.A. Variability of immunoregulatory and genetic markers in conditions of the combined effects of industrial environmental factors. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2016; 95(1): 45–8. https://elibrary.ru/vosqrn (in Russian)

27. Kazitskaya A.S., Yadykina T.K., Doroshilova A.V., Zhukova A.G. The role of polymorphic loci of cytokine genes in the development of atherosclerosis in miners with dust lung pathology. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2024; 103(7): 671–9. https://doi.org/10.47470/0016-9900-2024-103-7-671-679 https://elibrary.ru/nvsznw (in Russian)

28. Shevchenko A.V., Golovanova O.V., Konenkov V.I., Voevoda M.I., Maksimov V.N., Tolkacheva O.M. Analysis of correlation between the IL6 gene polymorphism (-174 G/C) and classic risk factors in patients with previous myocardial infarction. Meditsinskaya immunologiya. 2009; 11(6): 557–66. https://elibrary.ru/kxccen (in Russian)