TLR-4 Polymorphisms Shows The Genetic Susceptibility to Toxoplasmosis and Polycystic Ovary Syndrome
Haider Iskandar Flayh 1*, Al-Marsomy, Huda Dhaher 1, Khazaali, Enas Adnan Abdulrasol 2
Journal of Angiotherapy 8(4) 1-8 https://doi.org/10.25163/angiotherapy.849596
Submitted: 04 February 2024 Revised: 02 April 2024 Published: 08 April 2024
Abstract
Background: Toxoplasmosis, caused by Toxoplasma gondii, presents asymptomatic in healthy individuals but can lead to severe outcomes in immunocompromised individuals. Toll-like Receptors (TLRs) are crucial in recognizing pathogens like T. gondii. Specifically, TLR-4 gene polymorphisms (rs4986790, rs4986791) may influence susceptibility to toxoplasmosis and polycystic ovary syndrome (PCOS). Methods: A case-control study of 150 women categorized into PCOS + toxoplasmosis, PCOS only, toxoplasmosis only, and control groups. TLR-4 SNPs were examined using ARMS PCR. Results: TLR-4 rs4986790 showed no significant difference between PCOS + toxoplasmosis and PCOS only but correlated significantly with toxoplasmosis alone. Rs4986791 showed no significant correlation. Notably, the AG genotype of rs4986790 was more frequent among toxoplasmosis patients than controls, suggesting susceptibility. Discussion: Limited global research on this topic indicates conflicting findings. The rs4986790 SNP may affect TLR4 function, potentially through altered signaling pathways or ligand binding. Mutant TLR4's conformational changes could disrupt ligand docking and signaling pathways, reducing the immune response. Conclusion: The presence of the G allele within TLR-4 rs4986790 polymorphism may decrease TLR-4's interaction with T. gondii, reducing the immune response and increasing susceptibility to infection among AG genotype carriers.
Keyword: Toxoplasmosis, Polycystic ovary syndrome, Toll-like receptor 4, Gene polymorphisms, Susceptibility
References
Davoodi, N. R., Yousefi, J. V., Harzandi, N., Hajrafi, A., Rajaei, B., Gerayesh-Nejad, S., ... & Siadat, S. D. (2012). Molecular detection of methicillin resistant Staphylococcus aureus (MRSA) and methicillin resistant coagulase-negative Staphylococcus (CoNS) in Iran. Afr J Microbiol Res, 6(16), 3716-21.
Elmore, S. A., Jones, J. L., Conrad, P. A., Patton, S., Lindsay, D. S., & Dubey, J. P. (2010). Toxoplasma gondii: epidemiology, feline clinical aspects, and prevention. Trends in parasitology, 26(4), 190-196.
Ferwerda, B., McCall, M. B., Verheijen, K., Kullberg, B. J., Van Der Ven, A. J., Van der Meer, J. W., & Netea, M. G. (2008). Functional consequences of toll-like receptor 4 polymorphisms. Molecular medicine, 14, 346-352.
Glintborg, D. (2016). Endocrine and metabolic characteristics in polycystic ovary syndrome. Danish medical journal, 63(4), B5232.
Guo, R., Zheng, Y., Yang, J., & Zheng, N. (2015). Association of TNF-alpha, IL-6 and IL-1beta gene polymorphisms with polycystic ovary syndrome: a meta-analysis. BMC genetics, 16, 1-13.
Henckaerts, L., Pierik, M., Joossens, M., Ferrante, M., Rutgeerts, P., & Vermeire, S. (2007). Mutations in pattern recognition receptor genes modulate seroreactivity to microbial antigens in patients with inflammatory bowel disease. Gut, 56(11), 1536-1542.
Iwasaki, A., & Medzhitov, R. (2004). Toll-like receptor control of the adaptive immune responses. Nature immunology, 5(10), 987-995.
Khan, F. U., & Hussain, N. (2020). NH Serological and Molecular Based Diagnosis of Toxoplasma gondii in Galliformes by using ToxPK1 gene. Journal of Scientific Research in Medical and Biological Sciences, 1(2), 116-122.
Larsen, C. M., Faulenbach, M., Vaag, A., Vølund, A., Ehses, J. A., Seifert, B., ... & Donath, M. Y. (2007). Interleukin-1–receptor antagonist in type 2 diabetes mellitus. New England Journal of Medicine, 356(15), 1517-1526.
Tenter, A. M., Heckeroth, A. R., & Weiss, L. M. (2000). Toxoplasma gondii: from animals to humans. International journal for parasitology, 30(12-13), 1217-1258.Iwasaki A. and Medzhitov R. Regulation of adaptive immunity by the innate immune system. Science, 2010; 327: 291–295.
Theodoropoulos, G. E., Saridakis, V., Karantanos, T., Michalopoulos, N. V., Zagouri, F., Kontogianni, P., ... & Zografos, G. C. (2012). Toll-like receptors gene polymorphisms may confer increased susceptibility to breast cancer development. The Breast, 21(4), 534-538.
Wu, Y. (2011). The neuroimmunopharmacology of alcohol (Doctoral dissertation).
Wujcicka, W., Wilczynski, J., & Nowakowska, D. (2014). Do the placental barrier, parasite genotype and Toll-like receptor polymorphisms contribute to the course of primary infection with various Toxoplasma gondii genotypes in pregnant women?. European Journal of Clinical Microbiology & Infectious Diseases, 33, 703-709.
Wujcicka, W., Wilczynski, J., & Nowakowska, D. (2017). Genetic alterations within TLR genes in development of Toxoplasma gondii infection among Polish pregnant women. Advances in medical sciences, 62(2), 216-222.
Zainab Nur-Eldeen Aziz, Basil O. Saleh, (2024). Effect of Metformin and Vitamin D Supplementation on Metabolic and Hormonal Profiles in Polycystic Ovary Syndrome Women: A Follow-Up Study, Journal of Angiotherapy, 8(1), 1-7, 9438
Zangeneh, F. Z., Naghizadeh, M. M., & Masoumi, M. (2017). Polycystic ovary syndrome and circulating inflammatory markers. International Journal of Reproductive BioMedicine, 15(6), 375.
Zare-Bidaki, M., Hakimi, H., Abdollahi, S. H., Zainodini, N., Arababadi, M. K., & Kennedy, D. (2014). TLR4 in Toxoplasmosis; friends or foe?. Microbial pathogenesis, 69, 28-32.
Zeba Saleem, Abiha Ahmad Khan, Syeda Aamena Naaz et al., (2024). Polycystic Ovarian Syndrome: An Overview with Special Consideration to Its Oral and Pediatric Clinical Manifestations, Journal of Angiotherapy, 8(1), 1-7, 9415
Zhao, S., Tian, Y., Gao, X., Zhang, X., Liu, H., You, L., ... & Chen, Z. J. (2015). Family-based analysis of eight susceptibility loci in polycystic ovary syndrome. Scientific Reports, 5(1), 12619.
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