Original Articles
1 September 2025

Assessing tumor necrosis factor-α (-238 G/A and -308 G/A) genetic polymorphisms in sepsis susceptibility among cystic fibrosis patients

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Patients with cystic fibrosis are prone to recurrent bacterial infections, which eventually can cause critical sepsis and septic shock. Polymorphisms in tumor necrosis factor-α (TNF-α), as a pro-inflammatory cytokine, are implicated in its circulating levels and sepsis risk and development, particularly 308 G/A and -238 G/A. This investigation aims to assess the TNF-α (-238 G/A and -308 G/A) polymorphisms and sepsis risk in cystic fibrosis. A total of 120 cystic fibrosis patients were categorized into two groups: the septic and non-septic groups. Blood samples were harvested from participants, and DNA was extracted. The frequency of -238 G/A and -308 G/A TNF gene polymorphism was determined by polymerase chain reaction–restriction fragment length polymorphism. This investigation reported that heterozygous (GA) genotypes in the -238 G/A were more common among septic patients, 23 (38.33%), than non-septic patients, 13 (21.66%), and the same results were observed in -308 G/A; septic patients were 30 (50%), compared to non-septic patients, 13 (21.66%). Moreover, at the allelic level, the altered allele (A allele) was more commonly found in sepsis cystic fibrosis patients than in non-sepsis patients, with significant differences in both -308 G/A and -238 G/A. Our study concludes that TNF-α-238 and -308 (GA) polymorphism, as well as mutant (AA) genotypes, may be linked with a higher likelihood of developing sepsis in cystic fibrosis patients relative to those with the GG (wild-type) genotype.

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Bergougnoux A, Bareil C. CFTR gene variants, epidemiology and molecular pathology. Arch Pediatr 2020;27:eS8-12. DOI: https://doi.org/10.1016/S0929-693X(20)30044-0
Grosse J, Stehling F, Tschiedel E, et al. Bacteremia and fungaemia in cystic fibrosis patients with febrile pulmonary exacerbation: a prospective observational study. BMC Pulm Med 2017;17:96. DOI: https://doi.org/10.1186/s12890-017-0440-4
Choudhary C, Dugar S, Duggal A. Sepsis and septic shock: Guideline based management. Cleve Clin J Med 2020;87:53-64. DOI: https://doi.org/10.3949/ccjm.87a.18143
Stoller J, Halpin L, Weis M, et al. Epidemiology of severe sepsis: 2008-2012. J Crit Care 2016;31:58-62. DOI: https://doi.org/10.1016/j.jcrc.2015.09.034
Angus DC, Van der Poll T. Severe sepsis and septic shock. N Eng J Med 2013;369:840-51. DOI: https://doi.org/10.1056/NEJMra1208623
Van Loo G, Bertrand MJ. Death by TNF. A road to inflammation. Nat Rev Immunol 2023;23:289-303. DOI: https://doi.org/10.1038/s41577-022-00792-3
Varljen T, Rakic O, Sekulovic G. Association between tumor necrosis factor-α promoter-308 G/A polymorphism and early onset sepsis in preterm infants. Tohoku J Exp Med 2019;247:259-64. DOI: https://doi.org/10.1620/tjem.247.259
Wang D, Zhong X, Huang D, et al. Functional polymorphisms of interferon-gamma affect pneumonia-induced sepsis. PloS One 2014;9:e87049. DOI: https://doi.org/10.1371/journal.pone.0087049
Hugo Montes A, Valle-Garay E, Martin G, et al. The TNF-α (–238 G/A) polymorphism could protect against development of severe sepsis. Innate Immunity 2021;27:409-20. DOI: https://doi.org/10.1177/17534259211036186
Al-Mayah QS, Umayra AN, Hassan JS. Association of TNF-α-308G/A gene polymorphism with coronavirus disease-19 severity. Med J Babylon 2023;20:54-8. DOI: https://doi.org/10.4103/MJBL.MJBL_241_22
Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016;315:801-10. DOI: https://doi.org/10.1001/jama.2016.0287
Zidi S, Stayoussef M, Zouidi F, et al. Tumor necrosis factor alpha (− 238/− 308) and TNFRII-VNTR (− 322) polymorphisms as genetic biomarkers of susceptibility to develop cervical cancer among Tunisians. Pathol Oncol Res 2015;21:339-45. DOI: https://doi.org/10.1007/s12253-014-9826-2
Faricy LE, Church G. Sepsis and acute respiratory distress syndrome requiring extracorporeal life support in an adolescent with mild cystic fibrosis. Respir Med Case Rep 2017;22:235-7. DOI: https://doi.org/10.1016/j.rmcr.2017.09.002
Mansur A, Liese B, Steinau M, et al. The CD14 rs2569190 TT genotype is associated with an improved 30-day survival in patients with sepsis: a prospective observational cohort study. PLoS One 2015;10:e0127761. DOI: https://doi.org/10.1371/journal.pone.0127761
Abdellatif MA, Eyada E, Rabie W, et al. Genetic and biochemical predictors of neonatal bronchopulmonary dysplasia. J Pediatr Genet 2022;11:173-8. DOI: https://doi.org/10.1055/s-0040-1721740
Kassasseya C, Torsin LI, Musset C, et al. Divergent effects of tumor necrosis factor (TNF) in sepsis: a meta-analysis of experimental studies. Crit Care 2024;28:293. DOI: https://doi.org/10.1186/s13054-024-05057-0
Wang H, Guo S, Wan C, et al. Tumor necrosis factor-α− 308 G/A polymorphism and risk of sepsis, septic shock, and mortality: an updated meta-analysis. Oncotarget 2017;8:94910-9. DOI: https://doi.org/10.18632/oncotarget.20862
Georgescu AM, Banescu C, Azamfirei R, et al. Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression. BMC Infect Dis 2020;20:221. DOI: https://doi.org/10.1186/s12879-020-4910-6
Shimada T, Oda S, Sadahiro T, et al. Outcome prediction in sepsis combined use of genetic polymorphisms – a study in Japanese population. Cytokine 2011;54:79-84. DOI: https://doi.org/10.1016/j.cyto.2010.12.001
Kothari N, Bogra J, Abbas H. Tumor necrosis factor gene polymorphism results in high TNF levels in sepsis and septic shock. Cytokine 2013;61:676-81. DOI: https://doi.org/10.1016/j.cyto.2012.11.016
Song Z, Shen Y, Yao C, et al. Genetic variation in the TNF gene is associated with susceptibility to severe sepsis, but not with mortality. PLoS One 2012;7:e46113. DOI: https://doi.org/10.1371/journal.pone.0046113
Li R, Ye JJ, Gan L, et al. Traumatic inflammatory response: pathophysiological role and clinical value of cytokines. Eur J Trauma Emerg Surg 2023;50:1313-30. DOI: https://doi.org/10.1007/s00068-023-02388-5
Saleh A, Sultan A, Elashry M. Association of TNF-α G-308 a promoter polymorphism with the course and outcome of COVID-19 patients. Immunol Invest 2022;51:546-57. DOI: https://doi.org/10.1080/08820139.2020.1851709
Liang J, Su Y, Wang N, et al. A meta-analysis of the association between inflammatory cytokine polymorphism and neonatal sepsis. PLoS One 2024;19:e0301859. DOI: https://doi.org/10.1371/journal.pone.0301859
Coutinho CA, Marson F, Marcelino A, et al. TNF-alpha polymorphisms as a potential modifier gene in the cystic fibrosis. Int J Mol Epidemiol Genet 2014;5:87-99.

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Assessing tumor necrosis factor-α (-238 G/A and -308 G/A) genetic polymorphisms in sepsis susceptibility among cystic fibrosis patients. (2025). Italian Journal of Medicine. https://doi.org/10.4081/itjm.2025.2021

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