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Abstract
Background: Urinary tract infection UTI is one of the most common bacterial infection , predominantly caused by E.Coli this case control study aimed to evaluate demographic characteristic ,hematological parameters ,serum interleukin IL-6 and associated of TLR4 gene polymorphism (rs4986790 and rs4986791) with susceptibility to UTI Aim:To evaluated demographic characteristics inflammatory and hematological parameters ,serum ;IL-6 levels and the association of TLR4 gene polymorphism (rs 4986790 and rs 4986791). Methods:A total of 66 UTI patients and 55 healthy control were enrolled demographic data ,complete blood count , C–reactive protein CRP , urine analysis finding and serum IL-6 level were measured .TLR4 polymorphism were determining using PCR-RFLP , and Statistical analysis including odds ratios , 95% confidences intervals and effect size estimation .Results: No significant differences were found between patients and control healthy age or sex distribution (p > 0.05). UTI patients exhibited significantly elevate white blood cell counts, urinary red blood, neutrophil percentages, CRP levels, cells, and pus cells compared to controls (p < 0.001). Hemoglobin levels were lower in patients; however, this difference was not statistically significant (p = 0.08). serum IL-6 were markedly increased in UTI patients (47.9 ± 17.6 pg/mL) .compared with control (10.4 ± 4.8 pg/mL), indicated strong statistical significant p < 0.001 and a large effect size (Cohen’s d = 2.65). Genotype and allele distributions of TLR4 rs4986790 (Asp299Gly) and rs4986791 (Thr399Ile) did not demonstrate statistically significant associations with UTI susceptibility (p > 0.05) .Conclusion: UTI patients showed significant systemic and local inflammatory responses compared to healthy controls. TLR4 polymorphisms (rs4986790 and rs4986791) were not significantly associated with UTI susceptibility. These results highlight the diagnostic value of inflammatory markers, particularly IL-6, and suggest further studies on host genetic factors.
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Copyright (c) 2026 Hayder A. Ali

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References
- J. J. Zorc et al., "Clinical and demographic factors associated with urinary tract infection in young febrile infants," Pediatrics, vol. 116, no. 3, pp. 644-648, 2005. https://doi.org/10.1542/peds.2004-1919.
- W. E. Stamm and S. R. Norrby, "Urinary tract infections: disease panorama and challenges," the Journal of infectious diseases, vol. 183, no. Supplement_1, pp. S1-S4, 2001.
- T. K. Mattoo, N. Shaikh, and C. P. Nelson, "Contemporary management of urinary tract infection in children," Pediatrics, vol. 147, no. 2, p. e2020012138, 2021. https://doi.org/10.1542/peds.2020-012138.
- N. Shaikh et al., "Does this child have a urinary tract infection?," Jama, vol. 298, no. 24, pp. 2895-2904, 2007.
- A. L. Flores-Mireles, J. N. Walker, M. Caparon, and S. J. Hultgren, "Urinary tract infections: epidemiology, mechanisms of infection and treatment options," Nature reviews microbiology, vol. 13, no. 5, pp. 269-284, 2015. https://doi.org/10.1038/nrmicro3432
- H. J. Choi et al., "Characteristics of Escherichia coli urine isolates and risk factors for secondary bloodstream infections in patients with urinary tract infections," Microbiology spectrum, vol. 10, no. 4, pp. e01660-22, 2022.
- Y. Zhou et al., "Urinary tract infections caused by uropathogenic Escherichia coli: mechanisms of I infection and treatment options," International journal of molecular sciences, vol. 24, no. 13, p. 10537, 2023.
- C. Svanborg, G. Godaly, and M. Hedlund, "Cytokine responses during mucosal infections: role in disease pathogenesis and host defence," Current opinion in microbiology, vol. 2, no. 1, pp. 99-103, 1999.
- J. Scheller, C. Garbers, and S. Rose-John, "Interleukin-6: from basic biology to selective blockade of pro-inflammatory activities," in Seminars in immunology, 2014, vol. 26, no. 1: Elsevier, pp. 2-12.
- C. A. Hunter and S. A. Jones, "IL-6 as a keystone cytokine in health and disease," Nature immunology, vol. 16, no. 5, pp. 448-457, 2015. 10.1038/ni.3153.
- M. Gaafar, A. E. Fakhr, and W. A. Mokhtar, "TOLL Like Receptor Type Four Gene Polymorphism in Neonatal Sepsis in Zagazig University Children’s Hospital," Zagazig University Medical Journal, vol. 27, no. 1, pp. 9-19, 2021.
- E. D. Papadimitraki, G. K. Bertsias, and D. T. Boumpas, "Toll like receptors and autoimmunity: a critical appraisal," Journal of autoimmunity, vol. 29, no. 4, pp. 310-318, 2007.
- W. L. Huang, Y. Xu, and S. P. Wan, "Association of Toll‐like 4 receptor gene polymorphism(rs4986790, rs4986791) with the risk of urinary tract infection: A systematic review and meta‐analysis," The Kaohsiung Journal of Medical Sciences, vol. 36, no. 3, pp. 206-211, 2020. https://doi.org/10.1002/kjm2.12156.
- B. Foxman, "Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden," Infectious Disease Clinics, vol. 28, no. 1, pp. 1-13, 2014.
- Y. Wu et al., "Diagnostic and therapeutic value of biomarkers in urosepsis," Therapeutic Advances in Urology, vol. 15, p. 17562872231151852, 2023.
- T. Tanaka, M. Narazaki, and T. Kishimoto, "IL-6 in inflammation, immunity, and disease," Cold Spring Harbor perspectives in biology, vol. 6, no. 10, p. a016295, 2014.
- A. M. Abdzaid, "Association of SNPs in the TLR4 gene (rs4986790, rs4986791) with Susceptibility to Active TB in Iraqi Population," Journal of Scientific Research in Medical and Biological Sciences, vol. 5, no. 1, pp. 37-45, 2024.
- M. Ioana, B. Ferwerda, S. Farjadian, L. Ioana, A. Ghaderi, M. Oosting, L.A.B. Joosten, J.W.M. Van Der Meer, G. Romeo, D. Luiselli, D. Dediu, M.G. Netea, High variability of TLR4 gene in different ethnic groups in Iran, Innate Immun. 18 (2012) 492–502. https://doi.org/10.1177/1753425911423043.
- S. Akira, S. Uematsu, O. Takeuchi, Pathogen recognition and innate immunity, Cell. 124 (2006) 783–801. https://doi.org/10.1016/j.cell.2006.02.015.
- S. Ajdary, M.M. Ghamilouie, M.H. Alimohammadian, F. Riazi-Rad, S.R. Pakzad, Toll-like receptor 4 polymorphisms predispose to cutaneous leishmaniasis, Microbes Infect. 13 (2011) 226–231. https://doi.org/10.1016/j.micinf.2010.10.018.
- M. Ioana, B. Ferwerda, S. Farjadian, L. Ioana, A. Ghaderi, M. Oosting, L.A.B. Joosten, J.W.M. Van Der Meer, G. Romeo, D. Luiselli, D. Dediu, M.G. Netea, High variability of TLR4 gene in different ethnic groups in Iran, Innate Immun. 18 (2012) 492–502. https://doi.org/10.1177/1753425911423043.
- L.B. Barreiro, M. Ben-Ali, H. Quach, G. Laval, E. Patin, J.K. Pickrell, C. Bouchier, M. Tichit, O. Neyrolles, B. Gicquel, J.R. Kidd, K.K. Kidd, A. Alcaïs, J. Ragimbeau, S. Pellegrini, L. Abel, J.L. Casanova, L. Quintana-Murci, Evolutionary dynamics of human toll-like receptors and their different contributions to host defense, PLoS Genet. 5 (2009). https://doi.org/10.1371/journal.pgen.1000562.
- J. Karasneh, M. Bani-Hani, A. Alkhateeb, A. Hassan, F. Alzoubi, M. Thornhill, TLR2, TLR4 and CD86 gene polymorphisms in recurrent aphthous stomatitis, J. Oral Pathol. Med. 44 (2015) 857–863. https://doi.org/10.1111/jop.12298.
References
J. J. Zorc et al., "Clinical and demographic factors associated with urinary tract infection in young febrile infants," Pediatrics, vol. 116, no. 3, pp. 644-648, 2005. https://doi.org/10.1542/peds.2004-1919.
W. E. Stamm and S. R. Norrby, "Urinary tract infections: disease panorama and challenges," the Journal of infectious diseases, vol. 183, no. Supplement_1, pp. S1-S4, 2001.
T. K. Mattoo, N. Shaikh, and C. P. Nelson, "Contemporary management of urinary tract infection in children," Pediatrics, vol. 147, no. 2, p. e2020012138, 2021. https://doi.org/10.1542/peds.2020-012138.
N. Shaikh et al., "Does this child have a urinary tract infection?," Jama, vol. 298, no. 24, pp. 2895-2904, 2007.
A. L. Flores-Mireles, J. N. Walker, M. Caparon, and S. J. Hultgren, "Urinary tract infections: epidemiology, mechanisms of infection and treatment options," Nature reviews microbiology, vol. 13, no. 5, pp. 269-284, 2015. https://doi.org/10.1038/nrmicro3432
H. J. Choi et al., "Characteristics of Escherichia coli urine isolates and risk factors for secondary bloodstream infections in patients with urinary tract infections," Microbiology spectrum, vol. 10, no. 4, pp. e01660-22, 2022.
Y. Zhou et al., "Urinary tract infections caused by uropathogenic Escherichia coli: mechanisms of I infection and treatment options," International journal of molecular sciences, vol. 24, no. 13, p. 10537, 2023.
C. Svanborg, G. Godaly, and M. Hedlund, "Cytokine responses during mucosal infections: role in disease pathogenesis and host defence," Current opinion in microbiology, vol. 2, no. 1, pp. 99-103, 1999.
J. Scheller, C. Garbers, and S. Rose-John, "Interleukin-6: from basic biology to selective blockade of pro-inflammatory activities," in Seminars in immunology, 2014, vol. 26, no. 1: Elsevier, pp. 2-12.
C. A. Hunter and S. A. Jones, "IL-6 as a keystone cytokine in health and disease," Nature immunology, vol. 16, no. 5, pp. 448-457, 2015. 10.1038/ni.3153.
M. Gaafar, A. E. Fakhr, and W. A. Mokhtar, "TOLL Like Receptor Type Four Gene Polymorphism in Neonatal Sepsis in Zagazig University Children’s Hospital," Zagazig University Medical Journal, vol. 27, no. 1, pp. 9-19, 2021.
E. D. Papadimitraki, G. K. Bertsias, and D. T. Boumpas, "Toll like receptors and autoimmunity: a critical appraisal," Journal of autoimmunity, vol. 29, no. 4, pp. 310-318, 2007.
W. L. Huang, Y. Xu, and S. P. Wan, "Association of Toll‐like 4 receptor gene polymorphism(rs4986790, rs4986791) with the risk of urinary tract infection: A systematic review and meta‐analysis," The Kaohsiung Journal of Medical Sciences, vol. 36, no. 3, pp. 206-211, 2020. https://doi.org/10.1002/kjm2.12156.
B. Foxman, "Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden," Infectious Disease Clinics, vol. 28, no. 1, pp. 1-13, 2014.
Y. Wu et al., "Diagnostic and therapeutic value of biomarkers in urosepsis," Therapeutic Advances in Urology, vol. 15, p. 17562872231151852, 2023.
T. Tanaka, M. Narazaki, and T. Kishimoto, "IL-6 in inflammation, immunity, and disease," Cold Spring Harbor perspectives in biology, vol. 6, no. 10, p. a016295, 2014.
A. M. Abdzaid, "Association of SNPs in the TLR4 gene (rs4986790, rs4986791) with Susceptibility to Active TB in Iraqi Population," Journal of Scientific Research in Medical and Biological Sciences, vol. 5, no. 1, pp. 37-45, 2024.
M. Ioana, B. Ferwerda, S. Farjadian, L. Ioana, A. Ghaderi, M. Oosting, L.A.B. Joosten, J.W.M. Van Der Meer, G. Romeo, D. Luiselli, D. Dediu, M.G. Netea, High variability of TLR4 gene in different ethnic groups in Iran, Innate Immun. 18 (2012) 492–502. https://doi.org/10.1177/1753425911423043.
S. Akira, S. Uematsu, O. Takeuchi, Pathogen recognition and innate immunity, Cell. 124 (2006) 783–801. https://doi.org/10.1016/j.cell.2006.02.015.
S. Ajdary, M.M. Ghamilouie, M.H. Alimohammadian, F. Riazi-Rad, S.R. Pakzad, Toll-like receptor 4 polymorphisms predispose to cutaneous leishmaniasis, Microbes Infect. 13 (2011) 226–231. https://doi.org/10.1016/j.micinf.2010.10.018.
M. Ioana, B. Ferwerda, S. Farjadian, L. Ioana, A. Ghaderi, M. Oosting, L.A.B. Joosten, J.W.M. Van Der Meer, G. Romeo, D. Luiselli, D. Dediu, M.G. Netea, High variability of TLR4 gene in different ethnic groups in Iran, Innate Immun. 18 (2012) 492–502. https://doi.org/10.1177/1753425911423043.
L.B. Barreiro, M. Ben-Ali, H. Quach, G. Laval, E. Patin, J.K. Pickrell, C. Bouchier, M. Tichit, O. Neyrolles, B. Gicquel, J.R. Kidd, K.K. Kidd, A. Alcaïs, J. Ragimbeau, S. Pellegrini, L. Abel, J.L. Casanova, L. Quintana-Murci, Evolutionary dynamics of human toll-like receptors and their different contributions to host defense, PLoS Genet. 5 (2009). https://doi.org/10.1371/journal.pgen.1000562.
J. Karasneh, M. Bani-Hani, A. Alkhateeb, A. Hassan, F. Alzoubi, M. Thornhill, TLR2, TLR4 and CD86 gene polymorphisms in recurrent aphthous stomatitis, J. Oral Pathol. Med. 44 (2015) 857–863. https://doi.org/10.1111/jop.12298.
