ANALYSIS OF ASSOCIATION BETWEEN THE POLYMORPHIC VARIANTS OF THE TLR2 (RS5743708) AND TLR4 (RS4986790, RS4986791) GENES WITH THE HEALTH STATUS OF APPARENTLY HEALTHY INDIVIDUALS
Тhe study of single-nucleotide polymorphisms of Toll-like receptors has an important applied and theoretical value for revealing the mechanisms in formation of immunity features and its correction. The aim of the research was to study the available frequency of polymorphic variants of the TLR2 gene (rs5743708) and 896A/G (rs4986790), 1196C/T (rs4986791) of the TLR4 gene, and to assess the association with the health status of apparently healthy individuals. Materials and methods: the study involved 114 Caucasian individuals living in Poltava or Poltava oblast for a minimum of 2 years, who underwent the collection of anamnestic data, as well as the data of objective and clinical examinations. The polymorphic sites of the TLR2 (rs5743708) and TLR4 genes (rs4986790, rs4986791) were determined by polymerase chain reaction (PCR) followed by analysis of the restriction fragments length of the PCR products. The results of distribution of polymorphic variants 2258G/A in the genotypes of the TLR2 gene (rs5743708), 896A/G of the TLR4 gene (rs4986790), and 1196C/T of the TLR4 gene (rs4986791) corresponded to the theoretically expected ones at the Hardy-Weinberg equilibrium (χ2 = 0.02, р = 0.99; χ2 = 0.29, р = 0.86; χ2 = 1.46, р = 0.48, respectively). When comparing the presence of individual clinical manifestations that were detected during the interviewing, with the presence of polymorphic alleles in the genotype, a reliable relationship was established between the presence of the A allele in the polymorphic version of the TLR2 gene (rs5743708) in the genotype with rheumatism (p = 0.05), pyelonephritis (p = 0.05) and a bad habit of smoking (p = 0.04).
2. Receptors of congenital immunity: approaches to quantitative and functional evaluation of Toll-like human receptors / L.V. Kovalchuk, M.V. Khorev, A.S. Varivoda [and others] // Immunology. – 2008. – № 4. – P. 223-227.
3. Toll-like receptor 4 gene (TLR4), but not TLR2, polymorphisms modify the risk of tonsillar disease due to Streptococcus pyogenes and Haemophilus influenzae / Liadaki K., Petinaki E., Skoulakis C. [et al.] // Clin. Vaccine Immunol. – 2011. – Vol. 18, N. 2. – P. 217-222.
4. TLR4 896A/G gene polymorphism, rather than the TLR4 1196C/T and TLR2 2258G/A gene polymorphisms, determines the severe and aggravated course of atopic dermatitis in children / L.Yu. Levchenko, O.V. Izmailova, O.A. Shlykova, I.P. Kaidashev // Cytology and Genetics. – 2013. – Vol. 47, № 3. – P. 46-53.
5. The role of polymorphisms of Toll-like receptors genes 2, 4 and Clara cells in the development of bronchial asthma in adults / N.V. Lyakhovskaya, O.V. Izmailova, O.A. Shlykova, I.P. Kaidashev // Problems of ecology and medicine. – 2013. – Vol. 17, № 5-6. – P. 71-75.
6. Relationship of TLR2 and TLR4 gene polymorphism with a penchant for individual urogenital infections / Izmaĭlova O.V., Shlykova O.A., Bobrova N.O., Kaĭdashev I.P. // Tsitol Genet. – 2011. – Vol. 45, № 4. – P. 29-35.
7. . 2011 Sep-Oct;(5):83-6.
8. Role of several periodontopathogenic microorganisms and tlr4 gene Asp299Gly polymorphism in atherosclerosis pathogenesis / Skochko O.V., Bobrova N.A., Izmaylova O.V, Kaĭdashev I.P. // Zh Mikrobiol Epidemiol Immunobiol. – 2011. – № 5. – P. 83-86.
9. Sakevich V.D. The prevalence of haplotypes of TLR2, TLR4, CLC-10 polymorphic genes and their association with individual immunological parameters in patients with allergic rhinitis / V.D. Sakevich // Problems of ecology and medicine. – 2013. – Vol. 17, № 5-6. – P. 16-23.
10. Different patterns of Toll-like receptor 2 polymorphisms in populations of various ethnic and geographic origins / M. Ioana, B. Ferwerda, T.S. Plantinga [et all.] // Infect. Immun. – 2012. – Vol. 80, No. 5. – P. 1917-1922.
11. Genetic factors (genes of receptors of congenital immunity – TLRs) in the pathogenesis of atherosclerosis and its complications / I.I. Zhidkova, A.V. Ponasenko, M.V. Khutornaya [et al] // Medical immunology. – 2017. – Т. 19, № 3. – P. 241-254.
12. TLR4 polymorphisms and ageing: implications for the pathophysiology of age-related diseases / C.R. Balistreri, G. Colonna-Romano, D. Lio, [et al.] // J. Clin. Immunol. – 2009. – Vol. 29. – P. 406-415.
13. The Toll-like receptor 4 (Asp299Gly) polymorphism is a risk factor for gram-negative and haematogenous osteomyelitis / A.H. Montes, V. Asensi, V. Alvarez [et al.] // J. Clin. Exp. Immunol. – 2006. – Vol. 143 (3). – P. 404-413.
14. Erridge C. Monocytes heterozygous for the Asp299Gly and Thr399Ile mutations in the Toll-like receptor 4 gene show no deficit in lipopolysaccharide signalling / C. Erridge, J. Stewart, I.R. Poxton // J. Exp. Med. – 2003. – Vol. 197 (12). – P.1787-1791.
15. Mode of access to the website: https://www.ncbi.nlm.nih.gov/snp/?term=TLR2.
16. Mode of access to the website: https://www.ensembl.org/Homo_sapiens/Variation/Population?db=core;r=4:153704665-153705665;v=rs5743708;vdb=variation;vf=3234468#population_freq_EUR.
17. Asp299Gly Polymorphism of the TLR-4 Gene in Adult Patients with Fixed and with Reversible Airflow Obstruction in the Population of Crimea, Ukraine / Yu. Bisyuk, A. Kurchenko, O. Akhtemiichuk [et al.] // J. of Allergy and Clin. Immunol. – 2017. – Vol. 139 (2). – P. AB198.
18. Mode of access to the website: https://www.ncbi.nlm.nih.gov/snp/?term=TLR4.
19. Mode of access to the website: https://www.ensembl.org/Homo_sapiens/Variation/Population?db=core;r=9:117712524-117713524;v=rs4986790;vdb=variation;vf=3210403.
20. Mode of access to the website: https://www.ensembl.org/Homo_sapiens/Variation/Population?db=core;r=9:117712824-117713824;v=rs4986791;vdb=variation;vf=3210404.