The importance of studying genetic polymorphism of TNFα -308 G/A in Helicobacter pylori infection

Background. Reactions caused by cytokine production are of particular importance in the development of inflammation in H. pylori infection. The gene polymorphisms determine the corresponding protein production level, which affects the outcomes of inflammatory processes. In H. pyloriassociated gastritis, proinflammatory cytokines predominate. In the work were the TNFα gene polymorphisms analyzed.

The aim is to study the effect of TNFα -308 G/A (rs1800629) gene polymorphisms on the clinical features of H.pylori infection in a large industrial center of Russia.

Materials and methods. TNFα gene polymorphisms in patients with different forms of H. pylori infection were determined by allele-specific PCR.

Results. It was found that the risk of H. pylori associated diseases is higher in carriers of the GG TNFα – 308 G/A genotype. This genotype is characteristic of patients with erosive and ulcerative processes in the mucous membrane of stomach and duodenum. The risk of developing atrophic gastritis when infected with H. pylori is associated with the A allele and the GA genotype.

Conclusions. The study of the TNFα -308 G/A genetic polymorphisms makes it possible to identify individuals with a high risk of H. pylori infection, the occurrence of destructive diseases of stomach and duodenum, and those at risk of developing precancerous mucosal changes in the form of atrophic H. pylori-associated gastritis in order to provide timely prevention and treatment.

1. Sugano K., Tack J, Kuipers E. J. et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015; 64 (9): 1353–1367. DOI: 10.1136/gutjnl-2015–309252

2. Malfertheiner P., Megraud F., Rokkas T., et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022; 71: 1724–1762. DOI: 10.1136/gutjnl-2022–327745.

3. Butt J., Epplein M. How do global trends in Helicobacter pylori prevalence inform prevention planning? The lancet. Gastroenterology & hepatology. 2023; 8(6): 498–499. URL: https://doi.org/10.1016/S2468–1253(23)00101-2. Date of access: 02.09.2025.

4. Bordin D., Kuznetsova E., Stauver E., et al. Prevalence of Helicobacter pylori infection in various diseases and cohort studies conducted in the Russian Federation from 1990 to 2023: a systematic review. Effective Pharmacotherapy. 2024; 20 (30): 24–33. DOI:1 0.33978/2307-3586-2024-20-30-24-33.

5. Li Y., Choi H., Leung K. et al. Global prevalence of Helicobacter pylori infection between 1980 and 2022: a systematic review and meta-analysis. The Lancet. Gastroenterology & hepatology. 2023; 8(6): 553–564. URL: https://doi.org/10.1016/S2468– 1253 (23) 00070-5. Date of access:28.08.2025.

6. Cho J., Prashar A., Jones N. L., Moss S. F. Helicobacter pylori infection. Gastrointestinal Endoscopy Clinics of North America. 2021; 50(2): 261–282. URL: https://doi.org/10.1016/j.gtc.2021.02.001. Date of access: 05.08.2025.

7. Kim J., Wang T. C. Helicobacter pylori and Gastric Cancer. Gastrointestinal Endoscopy Clinics of North America. 2021; 31(3): 451–465. URL: https://doi.org/10.1016/j.giec.2021.03.003. Date of access: 17.09.2025.

8. Salvatori S., Marafini I., Laudisi F. Monteleone G. & Stolfi C. Mechanisms of Helicobacter pylori in gastric cancer. International Journal of Molecular Sciences. 2023; 24(3), 2895–2899. URL: https://doi.org/10.3390/ijms24032895. Date of access: 07.08.2025.

9. Senchukova M. A. Helicobacter pylori and Its Role in the Progression of Gastric Cancer. Current Microbiology. 2022;79(12):383. URL: https://doi.org/10.1007/s00284-022-03089-9. Date of access: 26.09.2025.

10. Cheung K. S., Leung W. K. Risk of gastric cancer development after eradication of Helicobacter pylori. World Journal of Gastrointestinal Oncology. 2021; 10 (5): 115–123. DOI: 10.4251/wjgo.v10.i5.115. URL: https://pubmed.ncbi.nlm.nih.gov/29770171. Date of access:01.10.2025.

11. Di Rocco A., Petrucci L., Assanto G. M. et al. Extranodal marginal zone lymphoma: Pathogenesis, Diagnosis, and Treatment. Cancers (Basel). 2022; 14(7): 1742. DOI: 10.3390/cancers14071742. Date of access: 12.09.2025.

12. Akbiyeva D. S. The Role of Cytokines in the Development of Gastroduodenal Diseases // Modern Problems of Science and Education. 2017; 2. URL: https://science-education.ru/ru/article/view?id=26324. Date of access: 07.10.2025.

13. Karbalaei M., Khorshidi M., Sisakht-pour B. et al. What are the effects of IL-1β (rs1143634), IL-17A promoter (rs2275913) and TLR 4 (rs4986790) gene polymorphism on the outcomes of infection with H. pylori; A systematic review and meta-analysis //Gene Reports. 2020; 20: 100735. DOI:10.1016/j.genrep.2020.100735

14. Tereshchenko I. V., Kayushev P. E. Tumor necrosis factor α and its role in pathology. Breast cancer. Medical review. 2022; 6(9): 523–527. DOI: 10.32364/2587-6821-2022-6-9-523-527. Date of access: 10.09.2025.

15. Suganuma M., Watanabe T., Sueoka E. et al. Role of TNF-α-Inducing Protein Secreted by Helicobacter pylori as a Tumor Promoter in Gastric Cancer and Emerging Preventive Strategies. Toxins. 2021; 13(3): 181. DOI: 10.3390/toxins13030181.

16. Perfilova K. M., Neumoina N. V., Butina T. Yu., et al. Experience of using the polymerase chain reaction method for the study of Helicobacter pylori markers. Med. Almanac. 2016; 42 (2): 52–56. (In Russ.) https://cyberleninka.ru/article/n/opyt-ispolzovaniya-metoda-polimeraznoy-tsepnoy-reaktsii-dlya-issledovaniya-markerov-helisobacter-pylori. Date of access: 01.08.2025.

17. Rebrova O. Y. Statistical analysis of medical data. Application of the STATISTICA software package, Moscow: Media Sfera, 2003. 312. (in Russ.). URL: https://djvu.online/file/TnHmracvcRO90?ysclid=lptyl9crio49137 Date of access: 01.08.2025.

18. Sugimoto M., Furuta T., Yamaoka Y. Influence of inflammatory cytokine polymorphisms on eradication rates of Helicobacter pylori. Journal of Gastroenterology and Hepatology. 2009; 24(11), 1725–1732. URL: https://pubmed.ncbi.nlm.nih.gov/20136959/ Date of access: 18.08.2025.

19. Qu Y., Wang X., Bai S. et al. The effects of TNF-α/TNFR 2 in regulatory T cells on the microenvironment and progression of gastric cancer. International Journal of Cancer. 2022; 150 (8), 1373–1391. DOI: 10.1002/ijc.33873. URL: https://pubmed.ncbi.nlm.nih.gov/34766338/ Date of access: 11.08.2025.

20. Hamajima N., Naito M., Kondo T., Goto Y. Genetic factors involved in the development of Helicobacter pylori related gastric cancer. Cancer Science. 2006; 97, 1129–1138. URL: URL: https://pubmed.ncbi.nlm.nih.gov/16879717/ Date of access: 07.06.2025.

21. Suganuma M., Watanabe T., Sueoka E. et al. Role of TNF-α-Inducing Protein Secreted by Helicobacter pylori as a Tumor Promoter in Gastric Cancer and Emerging Preventive Strategies. Toxins. 2021;13(3):181. DOI: 10.3390/toxins13030181.

22. Dincã A. L., Melit L. E., Mãrginean C. O. Old and new aspects of H.pylori-associated inflammation and gastric cancer. Children (Basel). 2022; 9(7): 1083–1088. DOI:

23. 3390/children9071083.

24. Zinina E. P., Tsarenko S. V., Logunov D. Y. et al. The role of proinflammatory and anti-inflammatory cytokines in bacterial pneumonia. Review. Annals of Critical Care. 2021; 1: 77–89 (in Russ.). DOI: 10.21320/1818–474X-2021-1-77-89 Date of access: 25.08.2025.

25. Shodieva М. Assessment of immune system parameters in children with gastroduodenal pathology. International Journal of Scientific Pediatrics. 2022; 1(7): 12–15. (In Russ.) https://doi.org/10.56121/2181-2926-2022-7-12-15. Date of access: 22.08.2025.

26. Kamalov Z. S., Abduzhabarova Z. M., Shodieva M. S. The role of genes-mediators of immune inflammation in destructive-inflammatory diseases of the gastroduodenal region in children. Doctor's Herald. 2021; 1 (2): 142–153 (in Russ.). https://doi.org/10.38095/2181–466X-2021992-141-152 Date of access: 25.08.2025.

27. Zhang J, Wang H. Morroniside protects against chronic atrophic gastritis in rat via inhibiting inflammation and apoptosis. Am J Transl Res. 2019; Sep 15; 11 (9): 6016–6023. PMID: 31632569; PMCID: PMC 6789209. Date of access: 07.10.2025.

28. Nezamzadeh F., Asadyun M., Anbiyaiee A. et al. Association of specific haplotype of tumor necrosis factor-α and interleukin-1β polymorphisms with Helicobacter pylori infection and gastric carcinogenesis. Germs. 2021; 11(4): 554–561. DOI: 10.18683/germs.2021.1290. URL: https://pubmed.ncbi.nlm.nih.gov/35096672/ Date of access:02.10.2025.