Toll-like Receptor 3 c.1377C/T and -7C/A Polymorphisms Associated with COVID-19 and COVID-19 Severity

Toll-like Receptor 3 c.1377C/T and -7C/A Polymorphisms Associated with COVID-19 and COVID-19 Severity

Chinese officials have reported the novel coronavirus to the world health organization, which is called the SARS-CoV-2. Toll-like receptor 3 (TLR3) induces antiviral immune responses via the production of type I interferons and inflammatory cytokines. In this study, we aimed to examine TLR3 c.1377C/T and -7C/A polymorphisms in COVID-19 and the association between some clinical parameters. We investigated the frequencies of TLR3 (c.1377C/T and -7C/A) polymorphisms in 150 patients with COVID-19 and 171 healthy individuals as controls. We performed polymerase chain reaction (PCR) based on restriction fragment length polymorphism (RFLP). We also investigated whether TLR3 c.1377C/T and-7C/A were associated with the severity of COVID-19. In addition, CHAID tree-based classification algorithm was created to investigate the severity of the patients in our study. TLR3 c.1377C/T TT genotype frequencies were statistically significant between cases and controls (p= 0.02). For TLR3 -7C/A polymorphism, the findings showed a statistically significant difference in A allele frequencies (p= 0.03). There was a statistically significant difference in the distribution of TLR3 -7C/A CA genotype frequency (p= 0.04). Our findings suggest that TLR3 c.1377C/T and -7C/A polymorphisms may be important on susceptibility or clinical course of COVID-19.

___

  • [1] Shang J., Wan Y., Liu C., Yount B., Gully K., Yang Y., Structure of mouse coronavirus spike protein complexed with receptor reveals mechanism for viral entry, PLoS Pathog, 3 (2020) 9-16.
  • [2] Chen Y., Liu Q., & Guo D., Emerging coronaviruses: genome structure, replication, and pathogenesis, Journal of Medical Virology, 92 (2020) 418-423.
  • [3] Gorbalenya A.E., Baker S.C., Baric R.S., Groot R.J., Drosten C., Gulyaeva A.A., The species severe acute respiratory syndrome related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2, Nat Microbiol., 5 (2020) 536–544.
  • [4] WHO 2022 (2022, February 23). Retrieved from https://www.who.int/emergencies/diseases/novel-coronavirus-2019
  • [5] Hoechter D.J., Becker-Pennrich A., Langrehr J., Bruegel M., Zwissler B., Schaefer S., Higher procoagulatory potential but lower DIC score in COVID-19 ARDS patients compared to non-COVID-19 ARDS patients, Thromb Res., 196 (2020) 186-192.
  • [6] Park S.E., Epidemiology, virology, and clinical features of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2; Coronavirus Disease-19), Clinical and Experimental Pediatric, 63(4) (2020) 119.
  • [7] Wu F., Zhao S., Yu B., Chen Y.M., Complete genome characterisation of a novel coronavirus associated with severe human respiratory disease in Wuhan, China, BioRxiv, (2020).
  • [8] Cui J., Li F., Shi Z.L., Origin and evolution of pathogenic coronaviruses, Nature Reviews Microbiology, 17(3) (2019) 181-192.
  • [9] Zhou P., Yang X.L., Wang X.G., Hu B., Zhang L., Zhang W., A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature, 579(7798) (2020) 270-273.
  • [10] Wan Y., Shang J., Graham R., Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus, Journal of Virology. 94(7) (2020) e00127-20.
  • [11] Wu J., & Chen Z.J,. Innate immune sensing and signaling of cytosolic nucleic acids, Annual review of immunology, 32 (2014) 461-488.
  • [12] Kawai T., & Akira S., The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors, Nature Immunology, 11(5) (2010) 373.
  • [13] Triantafilou M., Gamper FG., Haston RM., Mouratis MA., Morath S., Hartung T., et al. Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting, Journal of Biological Chemistry, 281(41) (2006) 31002-31011.
  • [14] Takeda K., Kaisho T., & Akira S., Toll-like receptors, Annual Review of Immunology, 21(1) (2003) 335-376.
  • [15] Matsumoto M., & Seya T., TLR3:interferon induction by double-stranded RNA including poly (I: C), Advanced Drug Delivery Reviews, 60(7) (2008) 805-812.
  • [16] Mukherjee S., Karmakar S., Babu S.P.S., TLR2 and TLR4 mediated host immune responses in major infectious diseases: a review, The Brazilian Journal of Infectious Diseases, 20(2) (2016) 193-204.
  • [17] Abdelwahab S.F., Hamdy S., Osman A.M., Zakaria Z.A., Association of the polymorphism of the Toll‐like receptor (TLR)‐3 and TLR‐9 genes with hepatitis C virus‐specific cell‐mediated immunity outcomes among Egyptian health‐care workers, Clinical & Experimental Immunology, 203(1) (2021) 3-12.
  • [18] Jin Y., Qiu S., Shao N., Zheng J., Association of toll-like receptor gene polymorphisms and its interaction with HPV infection in determining the susceptibility of cervical cancer in Chinese Han population, Mammalian Genome, 28(5) 2017 213-219.
  • [19] Engin A., Arslan S., Özbilüm N., Bakir M., Is there any relationship between Toll‐like receptor 3 c. 1377C/T and− 7C/A polymorphisms and susceptibility to Crimean Congo hemorrhagic fever?, Journal of medical virology, 88(10) (2016) 1690-1696.
  • [20] Frazao J.B., Errante P.R., Condino-Neto A., Toll-like receptors’ pathway disturbances are associated with increased susceptibility to infections in humans, Archivum Immunologiae et Therapiae Experimentalis, 61(6) 2013 427-443.
  • [21] Wang J., Liu Y., Liu Y., The association between TLR3 rs3775290 polymorphism and sporadic Parkinson’s disease in Chinese Han population, Neuroscience Letters, 728 (2020) 135005.
  • [22] Sengupta S., Mukherjee S., Bhattacharya N., & Tripathi A., Differential genotypic signatures of Toll-like receptor polymorphisms among dengue-chikungunya mono-and co-infected Eastern Indian patients, European Journal of Clinical Microbiology & Infectious Diseases, 40(7) (2021) 1369-1381.
  • [23] Zayed R.A., Omran D., Mokhtar D.A., 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., 96(3) (2017) 720–726.
  • [24] Alseoudy, M. M., Elgamal, M., Abdelghany, D. A., Borg, A. M., El-Mesery, A., Elzeiny, D., & Hammad, M. O., Prognostic impact of toll-like receptors gene polymorphism on outcome of COVID-19 pneumonia: A case-control study, Clinical Immunology (Orlando, Fla.), 235 (2022) 108929
  • [25] Huang X., Li H., Wang J., Huang C., Lu Y., Qin X., Genetic polymorphisms in Toll-like receptor 3 gene are associated with the risk of hepatitis B virus-related liver diseases in a Chinese population, Gene, 569(2) 2015 218-224.
  • [26] Mosaad Y.M., Metwally S.S., Farag R.E., Lotfy Z.F., AbdelTwab H.E., Association between toll-like receptor 3 (TLR3) rs3775290, TLR7 rs179008, TLR9 rs352140 and chronic HCV, Immunological Investigations, 48(3) (2019) 321-332.
  • [27] Zhou P., Fan L., Yu K.D., Zhao M.W., Toll‐like receptor 3 C1234T may protect against geographic atrophy through decreased dsRNA binding capacity, The FASEB Journal, 25(10) (2011) 3489-3495.
  • [28] Huik K., Avi R., Pauskar M., Kallas E., Jõgeda E.L., Karki T., Association between TLR3 rs3775291 and resistance to HIV among highly exposed Caucasian intravenous drug users, Infection, Genetics and Evolution, 20 (2013) 78-82.
  • [29] Akira S., Uematsu S., & Takeuchi O., Pathogen recognition and innate immunity, Cell, 124(4) (2006) 783-801.
  • [30] Habibabadi H.M., Parsania M., Pourfathollah A.A., 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., 22 (53) (2020) e20200026.
  • [31] Fan L., Zhou P., Hong Q., Chen A.X., Liu G.Y., Yu K.D., Toll-like receptor 3 acts as a suppressor gene in breast cancer initiation and progression: a two-stage association study and functional investigation, Oncoimmunology, 30 (2019) 8(6).
  • [32] Deeba E., Koptides D., Lambrianides A, Pantzaris M., Krashias G., Christodoulou C., Complete sequence analysis of human toll-like receptor 3 gene in natural killer cells of multiple sclerosis patients, Mult. Scler. Relat. Disord., 33 (2019) 100-106.
  • [33] Ye L., Chen B., Wang Y., Yang Y., Zeng J., Deng G., Prognostic value of liver biochemical parameters for COVID-19 mortality, Ann Hepatol, 21 (2021) 100279.
  • [34] Li J., Zhang Y., Wang F., Liu B., Li H., Tang G., Chang Z., Sex differences in clinical findings among patients with coronavirus disease 2019 (COVID-19) and severe condition, MedRxiv., (2020).
Cumhuriyet Science Journal-Cover
  • ISSN: 2587-2680
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 2002
  • Yayıncı: SİVAS CUMHURİYET ÜNİVERSİTESİ > FEN FAKÜLTESİ