Association of polymorphisms in TLR3 and TLR7 genes with susceptibility to COVID-19 among Iranian population: a retrospective case-control study
-
Masoud Parsania
,
Seyed Mahmood Seyed Khorrami
,
Mandana Hasanzad
,
Negar Parsania
,
Sina Nagozir
,
Narges Mokhtari
,
Hossein Mehrabi Habibabadi
,
Azam Ghaziasadi
,
Saber Soltani
,
Ali Jafarpour
,
Reza Pakzad
,
Seyed Mohammad Jazayeri
Abstract
Background and Objectives: Host genetic changes like single nucleotide polymorphisms (SNPs) are one of the main factors influencing susceptibility to viral infectious diseases. This study aimed to investigate the association between the host SNP of Toll-Like Receptor3 (TLR3) and Toll-Like Receptor7 (TLR7) genes involved in the immune system and susceptibility to COVID-19 in a sample of the Iranian population.
Materials and Methods: This retrospective case-control study evaluated 244 hospitalized COVID-19 patients as the case group and 156 suspected COVID-19 patients with mild signs as the control group. The genomic DNA of patients was genotyped for TLR7 (rs179008 and rs179009) and TLR3 (rs3775291 and rs3775296) SNPs using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
Results: A significant association between rs179008 SNP in the TLR7 gene and the susceptibility of COVID-19 was found between case and control groups. The AT genotype (Heterozygous) of TLR7 rs179008 A>T polymorphism showed a significant association with a 2.261-fold increased odds of COVID-19 (P=0.003; adjusted OR: 2.261; 99% CI: 1.117-4.575). In addition, a significant association between TC genotype of TLR7 rs179009 T>C polymorphism and increased odds of COVID-19 (P< 0.0001; adjusted OR: 6.818; 99% CI: 3.149-14.134) were determined. The polymorphism frequency of TLR3 rs3775291 and rs3775296 genotypes were not significantly different between the case and control groups (P> 0.004167).
Conclusion: SNPs in TLR7 rs179008 and rs179009 genotypes are considered host genetic factors that could be influenced individual susceptibility to COVID-19. The SNPs in TLR3 (rs3775296 and rs3775291) showed no significant association with COVID-19 in Iranian population.
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11. Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol 2014; 5: 461.
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18. Askar E, Ramadori G, Mihm S. Toll-like receptor 7 rs179008/Gln11Leu gene variants in chronic hepatitis C virus infection. J Med Virol 2010; 82: 1859-1868.
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20. Lester SN, Li K. Toll-like receptors in antiviral innate immunity. J Mol Biol 2014; 426: 1246-1264.
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25. Barkhash AV, Voevoda MI, Romaschenko AG. Association of single nucleotide polymorphism rs3775291 in the coding region of the TLR3 gene with predisposition to tick-borne encephalitis in a Russian population.
Antiviral Res 2013; 99: 136-138.
26. Ishizaki Y, Takemoto M, Kira R, Kusuhara K, Torisu H, Sakai Y, et al. Association of toll-like receptor 3 gene polymorphism with subacute sclerosing panencephalitis. J Neurovirol 2008; 14: 486-491.
27. Askar E, Bregadze R, Mertens J, Schweyer S, Rosenberger A, Ramadori G, et al. TLR3 gene polymorphisms and liver disease manifestations in chronic hepatitis C. J Med Virol 2009; 81: 1204-1211.
28. Zayed RA, Omran D, Mokhtar DA, Zakaria Z, Ezzat S, Soliman MA, et al. Association of Toll-like receptor 3 and Toll-like receptor 9 Single nucleotide polymorphisms with Hepatitis C virus infection and hepatic fibrosis in Egyptian patients. Am J Trop Med Hyg 2017; 96: 720-726.
29. Dhangadamajhi G, Rout R. Association of TLR3 functional variant (rs3775291) with COVID-19 susceptibility and death: a population-scale study. Hum Cell 2021; 34: 1025-1027.
30. Pati A, Padhi S, Chaudhury S, Panda AK. TLR3 (rs3775291) variant is not associated with SARS-CoV-2 infection and related mortality: a population-based correlation analysis. Hum Cell 2021; 34: 1274-1277.
31. Boghdadi G, Seleem WM. Differential expression of Toll-like receptors 7 & 8 mRNA in monocytes of patients with chronic hepatitis C infection: correlation with interferon and ribavirin treatment. Egypt J Immunol 2014; 21: 67-75.
32. Mosaad YM, Metwally SS, Farag RE, Lotfy ZF, AbdelTwab HE. Association between Toll-like receptor 3 (TLR3) rs3775290, TLR7 rs179008, TLR9 rs352140 and chronic HCV. Immunol Invest 2019; 48: 321-332.
33. Schoneveld AH, Hoefer I, Sluijter JP, Laman JD, de Kleijn DP, Pasterkamp G. Atherosclerotic lesion development and Toll like receptor 2 and 4 responsiveness. Atherosclerosis 2008; 197: 95-104.
34. Singh H, Samani D, Aggarwal S. TLR7 polymorphism (rs179008 and rs179009) in HIV-infected individual Naïve to art. Mediators Inflamm 2020; 2020: 6702169.
35. Mukherjee S, Tripathi A. Contribution of Toll like receptor polymorphisms to dengue susceptibility and clinical outcome among eastern Indian patients. Immunobiology 2019; 224: 774-785.
36. Teimouri H, Maali A. Single-nucleotide polymorphisms in host pattern-recognition receptors show association with antiviral responses against SARS-CoV-2, in-silico trial. J Med Microbiol Infect Dis 2020; 8: 65-70.
37. Zhu J, Zhang T, Cao L, Li A, Zheng K, Zhang N, et al. Toll like receptor7 polymorphisms in relation to disease susceptibility and progression in Chinese patients with chronic HBV infection. Sci Rep 2017; 7: 12417.
38. Funk E, Kottilil S, Gilliam B, Talwani R. Tickling the TLR7 to cure viral hepatitis. J Transl Med 2014; 12: 129.
39. Adalid-Peralta L, Godot V, Colin C, Krzysiek R, Tran T, Poignard P, et al. Stimulation of the primary anti-HIV antibody response by IFN-alpha in patients with acute HIV-1 infection. J Leukoc Biol 2008; 83: 1060-1067.
40. Chang JJ, Altfeld M. Innate immune activation in primary HIV-1 infection. J Infect Dis 2010; 202 Suppl 2(Suppl 2): S297-S301.
41. Zhang T, Zhu J, Su B, Cao L, Li Z, Wei H, et al. Effects of TLR7 polymorphisms on the susceptibility and progression of HIV-1 infection in Chinese MSM population. Front Immunol 2020; 11: 589010.
2. Chen Y, Liu Q, Guo D. Emerging coronaviruses: Genome structure, replication, and pathogenesis. J Med Virol 2020; 92: 418-423.
3. Ludwig S, Zarbock A. Coronaviruses and SARS-CoV-2: A brief overview. Anesth Analg 2020; 131: 93-96.
4. Ghafari M, Kadivar A, Katzourakis A. Excess deaths associated with the Iranian COVID-19 epidemic: A province-level analysis. Int J Infect Dis 2021; 107: 101-115.
5. Pouyan S, Bordbar M, Mohammadi Khoshoui M, Rahmanian S, Farajzadeh Z, Heidari B, et al. COVID-19: An analysis on official reports in Iran and the world along with some comparisons to other hazards. In: Pourghasemi HR, editor. Computers in Earth and Environmental Sciences: Elsevier; 2022. p. 635-654.
6. Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun 2020; 109: 102433.
7. Vabret N, Britton GJ, Gruber C, Hegde S, Kim J, Kuksin M, et al. Immunology of COVID-19: Current State of the Science. Immunity 2020; 52: 910-941.
8. Ovsyannikova IG, Haralambieva IH, Crooke SN, Poland GA, Kennedy RB. The role of host genetics in the immune response to SARS-CoV-2 and COVID-19 susceptibility and severity. Immunol Rev 2020; 296: 205-219.
9. Chowdhury MA, Hossain N, Kashem MA, Shahid MA, Alam A. Immune response in COVID-19: A review. J Infect Public Health 2020; 13: 1619-1629.
10. O'Neill LA, Golenbock D, Bowie AG. The history of Toll-like receptors - redefining innate immunity. Nat Rev Immunol 2013; 13: 453-460.
11. Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol 2014; 5: 461.
12. Kawai T, Akira S. Innate immune recognition of viral infection. Nat Immunol 2006; 7: 131-137.
13. Arpaia N, Barton GM. Toll-like receptors: key players in antiviral immunity. Curr Opin Virol 2011; 1: 447-454.
14. Chanock S. Candidate genes and single nucleotide polymorphisms (SNPs) in the study of human disease. Dis Markers 2001; 17: 89-98.
15. Liu F, Lu W, Qian Q, Qi W, Hu J, Feng B. Frequency of TLR 2, 4, and 9 gene polymorphisms in Chinese population and their susceptibility to type 2 diabetes and coronary artery disease. J Biomed Biotechnol 2012; 2012: 373945.
16. Wei X-S, Wei C-D, Tong Y-Q, Zhu C-L, Zhang P-A. Single nucleotide polymorphisms of toll-like receptor 7 and toll-like receptor 9 in hepatitis C virus infection patients from central China. Yonsei Med J 2014; 55: 428-434.
17. Yue M, Gao CF, Wang JJ, Wang CJ, Feng L, Wang J, et al. Toll-like receptor 7 variations are associated with the susceptibility to HCV infection among Chinese females. Infect Genet Evol 2014; 27: 264-270.
18. Askar E, Ramadori G, Mihm S. Toll-like receptor 7 rs179008/Gln11Leu gene variants in chronic hepatitis C virus infection. J Med Virol 2010; 82: 1859-1868.
19. Oh D-Y, Baumann K, Hamouda O, Eckert JK, Neumann K, Kücherer C, et al. A frequent functional toll-like receptor 7 polymorphism is associated with accelerated HIV-1 disease progression. AIDS 2009; 23: 297-307.
20. Lester SN, Li K. Toll-like receptors in antiviral innate immunity. J Mol Biol 2014; 426: 1246-1264.
21. Wong JP, Christopher ME, Viswanathan S, Dai X, Salazar AM, Sun L-Q, et al. Antiviral role of toll-like receptor-3 agonists against seasonal and avian influenza viruses. Curr Pharm Des 2009; 15: 1269-1274.
22. Means TK. Chapter 17 - Toll-Like Receptors in SLE. In: Lahita RG, editor. Systemic Lupus Erythematosus (Fifth Edition). San Diego: Academic Press; 2011. p. 293-306.
23. Sironi M, Biasin M, Cagliani R, Forni D, De Luca M, Saulle I, et al. A common polymorphism in TLR3 confers natural resistance to HIV-1 infection. J Immunol 2012; 188: 818-823.
24. Habibabadi HM, Parsania M, Pourfathollah AA, Haghighat S, Sharifi Z. Association of TLR3 single nucleotide polymorphisms with susceptibility to HTLV-1 infection in Iranian asymptomatic blood donors. Rev Soc Bras Med Trop 2020; 53: e20200026.
25. Barkhash AV, Voevoda MI, Romaschenko AG. Association of single nucleotide polymorphism rs3775291 in the coding region of the TLR3 gene with predisposition to tick-borne encephalitis in a Russian population.
Antiviral Res 2013; 99: 136-138.
26. Ishizaki Y, Takemoto M, Kira R, Kusuhara K, Torisu H, Sakai Y, et al. Association of toll-like receptor 3 gene polymorphism with subacute sclerosing panencephalitis. J Neurovirol 2008; 14: 486-491.
27. Askar E, Bregadze R, Mertens J, Schweyer S, Rosenberger A, Ramadori G, et al. TLR3 gene polymorphisms and liver disease manifestations in chronic hepatitis C. J Med Virol 2009; 81: 1204-1211.
28. Zayed RA, Omran D, Mokhtar DA, Zakaria Z, Ezzat S, Soliman MA, et al. Association of Toll-like receptor 3 and Toll-like receptor 9 Single nucleotide polymorphisms with Hepatitis C virus infection and hepatic fibrosis in Egyptian patients. Am J Trop Med Hyg 2017; 96: 720-726.
29. Dhangadamajhi G, Rout R. Association of TLR3 functional variant (rs3775291) with COVID-19 susceptibility and death: a population-scale study. Hum Cell 2021; 34: 1025-1027.
30. Pati A, Padhi S, Chaudhury S, Panda AK. TLR3 (rs3775291) variant is not associated with SARS-CoV-2 infection and related mortality: a population-based correlation analysis. Hum Cell 2021; 34: 1274-1277.
31. Boghdadi G, Seleem WM. Differential expression of Toll-like receptors 7 & 8 mRNA in monocytes of patients with chronic hepatitis C infection: correlation with interferon and ribavirin treatment. Egypt J Immunol 2014; 21: 67-75.
32. Mosaad YM, Metwally SS, Farag RE, Lotfy ZF, AbdelTwab HE. Association between Toll-like receptor 3 (TLR3) rs3775290, TLR7 rs179008, TLR9 rs352140 and chronic HCV. Immunol Invest 2019; 48: 321-332.
33. Schoneveld AH, Hoefer I, Sluijter JP, Laman JD, de Kleijn DP, Pasterkamp G. Atherosclerotic lesion development and Toll like receptor 2 and 4 responsiveness. Atherosclerosis 2008; 197: 95-104.
34. Singh H, Samani D, Aggarwal S. TLR7 polymorphism (rs179008 and rs179009) in HIV-infected individual Naïve to art. Mediators Inflamm 2020; 2020: 6702169.
35. Mukherjee S, Tripathi A. Contribution of Toll like receptor polymorphisms to dengue susceptibility and clinical outcome among eastern Indian patients. Immunobiology 2019; 224: 774-785.
36. Teimouri H, Maali A. Single-nucleotide polymorphisms in host pattern-recognition receptors show association with antiviral responses against SARS-CoV-2, in-silico trial. J Med Microbiol Infect Dis 2020; 8: 65-70.
37. Zhu J, Zhang T, Cao L, Li A, Zheng K, Zhang N, et al. Toll like receptor7 polymorphisms in relation to disease susceptibility and progression in Chinese patients with chronic HBV infection. Sci Rep 2017; 7: 12417.
38. Funk E, Kottilil S, Gilliam B, Talwani R. Tickling the TLR7 to cure viral hepatitis. J Transl Med 2014; 12: 129.
39. Adalid-Peralta L, Godot V, Colin C, Krzysiek R, Tran T, Poignard P, et al. Stimulation of the primary anti-HIV antibody response by IFN-alpha in patients with acute HIV-1 infection. J Leukoc Biol 2008; 83: 1060-1067.
40. Chang JJ, Altfeld M. Innate immune activation in primary HIV-1 infection. J Infect Dis 2010; 202 Suppl 2(Suppl 2): S297-S301.
41. Zhang T, Zhu J, Su B, Cao L, Li Z, Wei H, et al. Effects of TLR7 polymorphisms on the susceptibility and progression of HIV-1 infection in Chinese MSM population. Front Immunol 2020; 11: 589010.
| Files | ||
| Issue | Vol 16 No 1 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v16i1.14880 | |
| Keywords | ||
| TLR3; TLR7; Genetic polymorphism; COVID-19; Susceptibility | ||
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How to Cite
1.
Parsania M, Seyed Khorrami SM, Hasanzad M, Parsania N, Nagozir S, Mokhtari N, Mehrabi Habibabadi H, Ghaziasadi A, Soltani S, Jafarpour A, Pakzad R, Jazayeri SM. Association of polymorphisms in TLR3 and TLR7 genes with susceptibility to COVID-19 among Iranian population: a retrospective case-control study. Iran J Microbiol. 2024;16(1):114-123.
