Analysis of associations between polymorphic variants of some genes encoding transcription factors and the risk of developing vibration disease

UDC: 
613.644:575.174.015.3
DOI: 
10.21668/health.risk/2025.3.12.eng
Authors: 

G.F. Mukhammadiyeva1, E.R. Shaikhlislamova1,2, Yu.V. Ryabova1, E.F. Repina1, E.R. Kudoyarov1, D.O. Karimov1,3, D.A. Smolyankin1, D.D. Karimov1

Organization: 

1Ufa Research Institute of Occupational Health and Human Ecology, 94 Stepana Kuvykina Str., Ufa, 450106, Russian Federation
2Bashkir State Medical University, 3 Lenina Str., Ufa, 450008, Russian Federation
3N.A. Semashko National Research Institute of Public Health, 12 Vorontsovo Pole Str., build. 1, Moscow, 105064, Russian Federation

Abstract: 

This work assesses possible associations between polymorphisms of the IRX1, SMAD3, TEAD1 genes and the risk of developing vibration disease (VD), an occupational disease that occurs under prolonged exposure to industrial vibration.

The study involved 80 patients with VB and 105 people in the control group living in the Republic of Bashkortostan. Real-time polymerase chain reaction was used to genotype polymorphic variants of rs12653958 of the IRX1 gene, rs7163797 of the SMAD3 gene, and rs3993110 of the TEAD1 gene. Statistical data analysis was performed using the χ² criterion and calculation of the odds ratio (OR) with a 95 % confidence interval.

No significant associations were found between polymorphic variants rs12653958 of the IRX1 gene, rs7163797 of the SMAD3 gene, rs3993110 of the TEAD1 gene and the risk of developing VD. Although certain trends were observed in the distribution of genotype and allele frequencies, no statistically significant differences were found between the patient group and the control group. The most pronounced trend was noted for the polymorphic variant rs3993110 of the TEAD1 gene: the frequency of the A/A genotype in patients was 35.0 % versus 24.5 % in the control (p = 0.172).

The results of the study indicate that the studied polymorphic variants are probably not significant risk factors for the development of VD. However, the identified trends justify the need for further study on larger and ethnically heterogeneous samples. The obtained data expand the understanding of the molecular genetic basis of VD and can be used in developing personalized approaches to predicting the risk of developing occupational diseases. A promising direction is the study of additional genetic markers and their pathogenetic role in the development of the disease.

Keywords: 
vibration disease, occupational diseases, genetic polymorphisms, genetic predisposition, IRX1, SMAD3, TEAD1, risk
Mukhammadiyeva G.F., Shaikhlislamova E.R., Ryabova Yu.V., Repina E.F., Kudoyarov E.R., Karimov D.O., Smolyankin D.A., Karimov D.D. Analysis of associations between polymorphic variants of some genes encoding transcription factors and the risk of developing vibration disease. Health Risk Analysis, 2025, no. 3, pp. 114–121. DOI: 10.21668/health.risk/2025.3.12.eng
References: 
  1. Shaikhlislamova E.R., Valeeva E.T., Volgareva A.D., Kondrova N.S., Galimova R.R., Masyagutova L.M. Occupa-tional diseases caused by physical factors in the Republic of Bashkortostan. Meditsina truda i ekologiya cheloveka, 2018, no. 4 (16), pp. 63–69 (in Russian).
  2. Babanov S.A., Baraeva R.A., Budash D.S., Boguslavsky D.G. Professional polyneipropathies: differential diagnosis, expertise of professional suitability, medical rehabilitation and methods of physiotherapeutic exposure. Fizioterapevt, 2018, no. 4, pp. 37–49 (in Russian).
  3. Babanov S.A. Polyneuropathy syndrome in vibration disease from exposure to general vibration: assessment and pre-diction (place of electroneuromyography). Okhrana truda i tekhnika bezopasnosti na promyshlennykh predpriyatiyakh, 2020, no. 10, pp. 63–71. DOI: 10.33920/pro-4-2010-08 (in Russian).
  4. Zhukova A.G., Gorokhova L.G. A retrospective in molecular and genetic studies of production-related pathology. Meditsina v Kuzbasse, 2021, vol. 20, no. 3, pp. 5–11. DOI: 10.24412/2687-0053-2021-3-5-11 (in Russian).
  5. Baranov V.S. Genomics and predictive medicine. Sibirskii zhurnal klinicheskoi i eksperimental'noi meditsiny, 2021, vol. 36, no. 4, pp. 14–28. DOI: 10.29001/2073-8552-2021-36-4-14-28 (in Russian).
  6. Yadykina T.K., Korotenko O.Yu., Semenova E.A., Bugaeva M.S., Zhukova A.G. Study of glutathione-S-transferase (GST) T1 and M1 genes in aluminum industry workers with comorbid cardiovascular pathology, Meditsina truda i promyshlen-naya ekologiya, 2023, vol. 63, no. 8, pp. 519–527. DOI: 10.31089/1026-9428-2023-63-8-519-527 (in Russian).
  7. Küster M.M., Schneider M.A., Richter A.M., Richtmann S., Winter H., Kriegsmann M., Pullamsetti S.S., Stiewe T. [et al.]. Epigenetic Inactivation of the Tumor Suppressor IRX1 Occurs Frequently in Lung Adenocarcinoma and Its Silencing Is Associated with Impaired Prognosis. Cancers (Basel), 2020, vol. 12, no. 12, pp. 3528. DOI: 10.3390/cancers12123528
  8. Schepers D., Tortora G., Morisaki H., MacCarrick G., Lindsay M., Liang D., Mehta S.G., Hague J. [et al.]. A mutation update on the LDS-associated genes TGFB2/3 and SMAD2/3. Hum. Mutat., 2018, vol. 39, no. 5, pp. 621–634. DOI: 10.1002/humu.23407
  9. Hackinger S., Trajanoska K., Styrkarsdottir U., Zengini E., Steinberg J., Ritchie G.R.S., Hatzikotoulas K., Gilly A. [et al.]. Evaluation of shared genetic aetiology between osteoarthritis and bone mineral density identifies SMAD3 as a novel os-teoarthritis risk locus. Hum. Mol. Genet., 2017, vol. 26, no. 19, pp. 3850–3858. DOI: 10.1093/hmg/ddx285
  10. Cheng J., Wang S., Dong Y., Yuan Z. The Role and Regulatory Mechanism of Hippo Signaling Components in the Neuronal System. Front. Immunol., 2020, vol. 11, pp. 281. DOI: 10.3389/fimmu.2020.00281
  11. Cao X., Pfaff S.L., Gage F.H. YAP regulates neural progenitor cell number via the TEA domain transcription factor. Genes Dev., 2008, vol. 22, no. 23, pp. 3320–3334. DOI: 10.1101/gad.1726608
  12. Mukhtar T., Breda J., Grison A., Karimaddini Z., Grobecker P., Iber D., Beisel C., van Nimwegen E., Taylor V. Tead transcription factors differentially regulate cortical development. Sci. Rep., 2020, vol. 10, no. 1, pp. 4625. DOI: 10.1038/s41598-020-61490-5
  13. Hartmann S., Yasmeen S., Jacobs B.M., Denaxas S., Pirmohamed M., Gamazon E.R., Caulfield M.J., Genes & Health Research Team [et al.]. ADRA2A and IRX1 are putative risk genes for Raynaud's phenomenon. Nat. Commun., 2023, vol. 14, no. 1, pp. 6156. DOI: 10.1038/s41467-023-41876-5
  14. Sakaue S., Kanai M., Tanigawa Y., Karjalainen J., Kurki M., Koshiba S., Narita A., Konuma T. [et al.]. A cross-population atlas of genetic associations for 220 human phenotypes. Nat. Genet., 2021, vol. 53, no. 10, pp. 1415–1424. DOI: 10.1038/s41588-021-00931-x
  15. Koyama S., Ito K., Terao C., Akiyama M., Horikoshi M., Momozawa Y., Matsunaga H., Ieki H. [et al.]. Population-specific and trans-ancestry genome-wide analyses identify distinct and shared genetic risk loci for coronary artery disease. Nat. Genet., 2020, vol. 52, no. 11, pp. 1169–1177. DOI: 10.1038/s41588-020-0705-3
  16. Wang Y., Yu T., Jin H., Zhao C., Wang Y. Knockdown MiR-302b Alleviates LPS-Induced Injury by Targeting Smad3 in C28/I2 Chondrocytic Cells. Cell. Physiol. Biochem., 2018, vol. 45, no. 2, pp. 733–743. DOI: 10.1159/000487165
  17. Qu Y., Chen S., Han M., Gu Z., Zhang Y., Fan T., Zeng M., Ruan G. [et al.]. Osteoporosis and osteoarthritis: a bi-directional Mendelian randomization study. Arthritis Res. Ther., 2023, vol. 25, no. 1, pp. 242. DOI: 10.1186/s13075-023-03213-5
  18. Yao J.Y., Wang Y., An J., Mao C.-M., Hou N., Lv Y.-X., Wang Y.-L., Cui F. [et al.]. Mutation analysis of the Smad3 gene in human osteoarthritis. Eur. J. Hum. Genet., 2003, vol. 11, no. 9, pp. 714–717. DOI: 10.1038/sj.ejhg.5201034
  19. Yang H.-Y., Hu W.-H., Jiang T., Zhao H. SMAD3 gene rs12901499 polymorphism increased the risk of osteoarthritis. Biosci. Rep., 2018, vol. 38, no. 3, pp. BSR20180380. DOI: 10.1042/BSR20180380
  20. Miller C.L., Pjanic M., Wang T., Nguyen T., Cohain A., Lee J.D., Perisic L., Hedin U. [et al.]. Integrative functional genomics identifies regulatory mechanisms at coronary artery disease loci. Nat. Commun., 2016, vol. 7, pp. 12092. DOI: 10.1038/ncomms12092
  21. Samani N.J., Erdmann J., Hall A.S., Hengstenberg C., Mangino M., Mayer B., Dixon R.J., Meitinger T. [et al.]. Genomewide association analysis of coronary artery disease. N. Engl. J. Med., 2007, vol. 357, no. 5, pp. 443–453. DOI: 10.1056/NEJMoa072366
  22. Yao M., Wang Y., Zhang P., Chen H., Xu Z., Jiao J., Yuan Z. BMP2-SMAD signaling represses the proliferation of embryonic neural stem cells through YAP. J. Neurosci., 2014, vol. 34, no. 36, pp. 12039–12048. DOI: 10.1523/JNEUROSCI.0486-14.2014
  23. Yoshida T. MCAT elements and the TEF-1 family of transcription factors in muscle development and disease. Arte-rioscler. Thromb. Vasc. Biol., 2008, vol. 28, no. 1, pp. 8–17. DOI: 10.1161/ATVBAHA.107.155788
  24. Schrauwen I., Szelinger S., Siniard A.L., Corneveaux J.J., Kurdoglu A., Richholt R., De Both M., Malenica I. [et al.]. A De Novo Mutation in TEAD1 Causes Non-X-Linked Aicardi Syndrome. Invest. Ophthalmol. Vis. Sci., 2015, vol. 56, no. 6, pp. 3896–3904. DOI: 10.1167/iovs.14-16261
  25. Boer C.G., Hatzikotoulas K., Southam L., Stefánsdóttir L., Zhang Y., Coutinho de Almeida R., Wu T.T., Zheng J. [et al.]. Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations. Cell, 2021, vol. 184, no. 18, pp. 4784–4818.e17. DOI: 10.1016/j.cell.2021.07.038
Received: 
03.06.2025
Approved: 
23.07.2025
Accepted for publication: 
24.09.2025

You are here

Home