Single nucleotide polymorphisms of TLR-2, TLR-3, TLR-4 and susceptibility to inflammatory diseases of the respiratory tract
DOI:
https://doi.org/10.14739/2310-1210.2018.5.141527Keywords:
genotype, respiratory tract diseases, Arg753Gln polymorphism of TLR-2 gene, Leu412Phe of TLR-3 gene, Asp299Gly of TLR-4 geneAbstract
The aim of the research is to establish an association between Arg753Gln polymorphism of TLR-2 gene, Leu412Phe of TLR-3 gene, Asp299Gly of TLR-4 gene and susceptibility to inflammatory diseases of the upper and lower respiratory tract and the complicated forms of АRI development.
Materials and methods. 98 healthy subjects distributed according to the genotype of TLR-2, TLR-3, TLR-4 were enrolled in the study of association between Arg753Gln polymorphism of TLR-2, Leu412Phe of TLR-3 and Asp299Gly of TLR-4 genes and inflammatory diseases of the upper and lower respiratory tract. The polymorphic site of TLR-2 Arg753Gln, TLR-3 Leu412Phe and TLR-4 Asp299Gly genotyping was performed by polymerase chain reaction using oligonucleotide primers. The relative risk of the disease and complications development was estimated using the odds ratio with 95 % confidence interval. The statistical significance of differences in qualitative characteristics was evaluated using Fischer's exact test.
Results. It has been revealed that individuals with polymorphic TLR-2, TLR-3 and TLR-4 genes have an increased susceptibility to АRI with frequent episodes during the year that are complicated by lower respiratory tract inflammation as well as chronic inflammatory diseases of the upper respiratory tract. It has been shown that the risk of bronchitis and pneumonia development in АRIs is higher in subjects with polymorphic genotypes of TLR-2, TLR-3 and TLR-4 as compared to the carriers of normal alleles distribution: 2.9 times with Leu/Phe genotype of TLR-3, 20.0 times with Phe/Phe of TLR-3 and 12.8 times with combinations of polymorphic genotypes of TLR-2, TLR-3, TLR-4.
Conclusions. The results of the study indicate that the presence of single-nucleotide polymorphisms TLR-2 Arg753Gln, TLR-3 Leu412Phe and TLR-4 Asp299Gly is the marker of high susceptibility to respiratory diseases. Individuals with polymorphic status of TLR-2, TLR-3 and TLR-4 genotypes have an increased susceptibility to inflammatory diseases of the upper and lower respiratory tract with АRI frequency of 4 or more episodes during the year.
References
Khobzei, M. K., Holubovska, O. A., Lishchyshyna, O. M., Andreichyn, M. A., Batsyura, H. V., Hradil, H. H., et al. (2015). Nakaz Ministerstva okhorony zdorovia Ukrainy «Unifikovanyi klinichnyi protokol pervynnoi medychnoi dopomohy doroslym ta ditiam “Hostri respiratorni infektsii”» vid 16.06.2014 roku №499 [Order of the Ministry of Public Health of Ukraine «Unified clinical protocol of primary care for adults and children “Acute respiratory infections”» of June 16, 2014, №499]. Klinichna imunolohiia. Alerholohiia. Infektolohiia, 5–6(84–85), 33–40 [in Ukrainian].
Abaturov, A. Ye., Volosoveс, A. P., Yulish, Ye. I. (2012). Rol' TOLL-podobnykh reсeptorov v rekogniсii patogen-assoсiirovannykh molekulyarnykh struktur infekcionnykh patogennykh agentov i razvitii vospaleniya. Chast' 1. Semejstvo TLR [The role of Toll-like receptors in the recognition of pathogen-associated molecular structures of infectious pathogenic agents and the development of inflammation. Part 1. Family TLR]. Zdorov'ye rebenka, 5(40), 116–121 [in Russian].
Trejo-de la, O. A., Hernández-Sancén, P., & Maldonado-Bernal, C. (2014). Relevance of single-nucleotide polymorphisms in human TLR genes to infectious and inflammatory diseases and cancer. Genes and Immunity, 15(4), 199–209. doi: 10.1038/gene.2014.10.
Izmailova, O. V., Shlykova, O. A., Bobrova, N. O., & Kaidashev, I. P. (2009). Rol polimorfizmu Toll-podibnoho retseptora 4 Asp299Gly u rozvytku infektsii, shcho peredaiutsia statevym shliakhom [The role of Toll-like Asp299Gly receptor polymorphism in the development of sexually transmitted infections]. Problemy ekolohii ta medytsyny, 13(5–6), 3–6 [in Ukrainian].
Paulus, S. C., Hirschfeld, A. F., Victor, R. E., Brunstein, J., Thomas, E., & Turvey, S. E. (2007). Common human Toll-like receptor 4 polymorphisms: role in susceptibility to respiratory syncytial virus infection and functional immunological relevance. Clin. Immunol, 123(3), 252–7. doi: 10.1016/j.clim.2007.03.003.
Holmes, C. L., Russell, J. A., & Walley, K. R. (2003). Genetic Polymorphisms in Sepsis and Septic Shock: Role in Prognosis and Potential for Therapy Free To View. J. CHEST, 124(3), 1103–1115.
Ogus, A. C., Yoldas, B., Ozdemir, T., Ugus, A., Olcen, S., Keser, I., et al. (2004). The Arg753GIn polymorphism of the human toll-like receptor 2 gene in tuberculosis disease. Eur Respir J, 23(2), 219–223. doi: 10.1183/09031936.03.00061703.
Lorenz, E., Mira, J., Cornish, K., Arbour, N. C., & Schwartz, D. A. (2000). A novel polymorphism in the toll-like receptor 2 gene and its potential association with staphylococcal infection. Infect Immun, 68(11), 6398–6401. doi: 10.1128/IAI.68.11.6398-6401.2000.
Ishizaki, Y., Takemoto, M., Kira, R., Kusuhara, K., Torisu, H., Sakai, Y., et al. (2008). Association of Toll-like receptor 3 gene polymorphism with subacute sclerosing panencephalitis. Journal of NeuroVirology, 14(6), 486–491. doi: 10.1080/13550280802298120.
Gorbea, C., Makar, K. A., Pauschinger, M., Pratt, G., Bersola, J. L., Varela, J., et al. (2010). Role for Toll-like Receptor 3 Variants in Host Susceptibility to Enteroviral Myocarditis and Dilated Cardiomyopathy. Journal of Biological Chemistry, 285(30), 23208–23. 10.1074/ jbc.M109.047464
1074/jbc.M109.047464.
Dubinskaya, G., Pryimenko, N., Kaidashev, I., Pokhylko, V., & Chub, K. (2014). Rol' polimorfizma genov TLR-2, TLR-3, TLR-4 pri grippe [The role of tlr-2, tlr-3, tlr-4 genes polymorphism of grippe]. Gergian medical news, 7–8(232–233), 51–55 [in Russian].
Drutskaya, M. S., Nedospasov, S. A., & Belousov, P. V. (2011). Vrozhdennoe raspoznavanie virusov [Innate mechanisms of viral recognition]. Molekulyarnaya biologiya, 45(1), 7–19. [in Russian].
Kumar, H., Kawai, T., & Akira, S. (2009). Toll-like receptors and innate immunity. Biochem. Biophys. Res. Commun., 388(4), 621–5. doi: 10.1016/j.bbrc.2009.08.062.
Bairakova, A. L., Voropaeva, E. A., Afanasiev, S. S., AIeshkin, V. A., Nesvizhsky, Yu. V., Karaulov, A. V., et al. (2008). Rol' i biologicheskoe znachenie toll-podobnykh receptorov v antiinfekcionnoj rezistentnosti organizma [The role and biological significance of the Toll-like receptors in the anti-infective resistance of the organism]. Vestnik Rossijskoj akademii medicinskikh nauk, 1, 45–54. [in Russian].
Koval'chuk, L. V., Khoreva, M. V., Varivoda, A. S., Nikolaeva, I. N., Gracheva, L. A., Galukhina, Ye. R. et al. (2008). Oposredovannye cherez Toll-podobnye receptory vyrabotka citokinov i e'kspressiya poverkhnostnykh markerov lejkocitami cheloveka. [Mediated via Toll-like receptors production of cytokines and the expression of surface markers by human leukocytes]. Immunologiya, 4, 223–227. [in Russian].
Kono, H., Karmarkar, D., Iwakura, Y., & Rock, К. L. (2010). Identification of the Cellular Sensor That Stimulates the Inflammatory Response to Sterile Cell Death. J. Immunol., 184(8), 4470–4478. doi: 10.4049/jimmunol.0902485.
Malezhik, L. P., & Karpov, N. I. (2011). Vliyanie polimorfizma receptorov Toll-4 (Asp299Gly) i Toll-6 (Ser249Pro) na produkciyu citokinov u detej, chasto boleyushchikh ostrymi respiratornymi virusnymi infekciyami [Effect of Toll-4 (Asp299Gly) and Toll-6 (Ser249Pro) receptor polymorphism on the production of cytokines in children who frequently suffer from acute respiratory viral infections]. Vrach-aspirant, 6(49), 125–131. [in Russian].
Brown, R. A., Gralewski, J. H., Eid, A. J., Knoll, B. M., Finberg, R. W., & Razonable, R. R. (2010). R753Q Single Nucleotide Polymorphism Impairs Toll-like Receptor 2 Recognition of Hepatitis C Virus Core and Nonstructural 3 Proteins. Transplantation, 89(7), 811–815. doi: 10.1097/TP.0b013e3181cbac18.
Eid, A. J., Brown, R. A., Paya, C.V., & Razonable, R. R. (2007). Association between toll-like receptor polymorphisms and the outcome of liver transplantation for chronic hepatitis C virus. Transplantation, 84(4), 511–6. doi: 10.1097/01.tp.0000276960.35313.bf.
Dolganiuc, A., Oak, S, Kodys, K., Golenbock, D. T., Finberg, R. W., Kurt-Jones, E., & Szabo, G. (2004). Hepatitis C core and nonstructural 3 proteins trigger toll-like receptor 2-mediated pathways and inflammatory activation Gastroenterology, 127(5), 1513. doi: 10.1053/j.gastro.2004.08.067.
Schröder, N. W., Diterich, I., Zinke, A., Eckert, J., Draing, C., von Baehr, V., et al. (2005). Heterozygous Arg753Gln polymorphism of human TLR-2 impairs immune activation by Borrelia burgdorferi and protects from late stage Lyme disease. J. Immunol., 175(4), 2534–2540. doi: 10.4049/jimmunol.175.4.2534.
Tsai, Wan-Yu, & Ho, Mei. (2005). Polymorphisms of Toll-like Receptor 3 (TLR3), TNF Receptor-associated Factor 6 (TRAF6), and Heme Oxygenase-1 (HO-1) are Associated with Clinical Severity of Severe Acute Respiratory Syndrome. Retrieved from http://www. http://handle.ncl.edu.tw/11296/ndltd/87497652997228105336
Nahum, A., Dadi, H., Bates, A., & Roifman, C. M. (2012). The biological significance of TLR3 variant, L412F, in conferring susceptibility to cutaneous candidiasis, CMV and autoimmunity. Autoimmunity Reviews., 11(5), 341–347. doi: 10.1016/j.autrev.2011.10.007.
Downloads
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)