Abstract
Polymorphisms in toll-like receptors (TLRs) have been reported to increase susceptibility for some diseases. TLR-2 gene polymorphisms in Turkish children with recurrent respiratory tract infections and without well-known humoral immunodeficiencies were examined. The study consisted of 52 children with recurrent infections (study group) and 91 healthy children with a maximum of two infections in a year (control group). Recurrent infection was defined as the presence of at least six febrile bacterial infection episodes in a year. Not only TLR-2 gene polymorphisms but also immunoglobulins (IgG, IgM, IgA), IgG subsets (G1, G2, G3), and specific antibody levels (anti-tetanus and anti-hemophilus influenza) were determined to exclude humoral immunodeficiencies. The Arg753Gln and Arg677Trp polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism. The Arg753Arg genotype was significantly decreased in the study group compared to the control (P < 0.05). Children with recurrent infections were also found to be more frequently Arg753Gln heterozygous (P < 0.05), and their Gln allele distribution was higher than that of the control subjects (23% vs. 4.9%; P < 0.001). In contrast to these results, we did not detect any case with Arg677Trp polymorphism in both groups. These results have indicated that there is a strong significant relationship between susceptibility to recurrent bacterial infections and Arg753Gln polymorphism of the TLR-2 gene.
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Aksu G, Kutukculer N, Genel F, Koturoglu G, Kurugol Z (2006) Serum immunoglobulins (IgG, IgM, IgA) and IgG subclass concentrations in healthy children: a study using nephelometric technique. Turk J Pediatr 48:19–24
Arbour NC, Lorenz E, Schutte BC, Zabner J, Kline JN, Jones M, Frees K, Watt JL, Schwartz DA (2000) TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet 25:187–191
Badolato R, Fontana S, Barcella D, Moratto D, Dippolito C, Crovella S, Notarangelo LD, Duse M (2004) Toll-like receptor-4 genotype in children with respiratory infections. Allergy 59:1018–1019
Ben-Ali M, Barbouche MR, Bousnina S, Chabbou A, Dellagi K (2004) Toll-like receptor 2 Arg677Trp polymorphism is associated with susceptibility to tuberculosis in Tunisian patients. Clin Diagn Lab Immunol 11:625–626
Berdeli A, Celik HA, Ozyurek AR, Dogrusoz B, Aydin HH (2005) TLR-2 gene Arg753Gln polymorphism is strongly associated with acute rheumatic fever. J Mol Med 83:535–541
Breukels MA, Spanjaard L, Sanders LA, Rijkers GT (2001) Immunological characterization of conjugated Haemophilus influenza type b vaccine failure in infants. Clin İnfect Dis 32:1700–1705
Feterowski C, Emmanuilidis K, Miethke T, Gerauer K, Rump M, Ulm K, Holzmann B, Weihghardt B (2003) Effects of functional Toll-like receptor-4 mutations on the immune response to human and experimental sepsis. Immunology 109:426–431
Fitzgerald KA, Palsson-McDermott EM, Bowie AG, Jefferies JA, Mansell AS, Brady G, Brint E, Dunne A, Gray P, Harte MT, Mc Murray D, Smith DE, Sims JE, Bird TA, O’Neil LA (2001) Mal (MyD88-adapter-like) is required for toll-like receptor 4 signal transduction. Nature 413:78–83
Hawn TR, Verbon A, Lettinga KD, Zhao LP, Li SS, Laws RJ, Skerrett SJ, Beutler B, Schroeder B, Nachman A, Ozinsky A, Smith KD, Aderem A (2003) A common dominant TLR5 stop codon polymorphism abolishes flagellin signalling and is associated with susceptibility to Legionnaires’ disease. J Exp Med 198: 1563–1572
Horng T, Barton GM, Medzhitov R (2001) TIRAP: an adapter molecule in toll-like signaling pathway. Nat Immunol 2:835–841
Kadioğlu A, Andrew PW (2004) The innate immune response to pneumococcal lung infection: the untold story. Trends Immunol 25:142–149
Kang TJ, Chae GT (2001) Detection of Toll-like receptor 2 (TLR2) mutation in the lepramotous leprosy patients. FEMS Immunol Med Microbiol 31:53–58
Kiechl S, Lorenz E, Reindl M, Weidermann CJ, Oberhollenzer B, Bonora E, Willeit J, Schwartz DA (2002) Toll-like receptor 4 polymorphisms and atherogenesis. N Eng J Med 347: 185–192
Lorenz E, Mira JP, Cornish KL, Arbour NC, Schwartz DA (2000) A novel polymorphism in the toll-like receptor-2 gene and its potential association with staphylococcal infection. Infect Immun 68:6398–6401
Lorenz E, Hallman M, Marttila R, Haataja R, Schwartz DA (2002) Association between the Asp299Gly polymorphism in the Toll-like receptor 4 and premature births in the Finnish population. Pediatr Res 52:373–376
Lorenz E, Chemotti DC, Jiang AL, McDougal LD (2005) Differential involvement of Toll-like receptors 2 and 4 in the host response to acute respiratory infections with wild-type and mutant Haemophilus influenza strains. Infect Immun 73: 2075–2082
Medvedev AE, Lentschat A, Kuhns DB, Blanco JC, Salkowski C, Zhang S, Arditi M, Gallin JI, Vogel SN (2003) Distinct IRAK-4 confer hyporesponsiveness to lipopolysaccharide and interleukin-1 in a patient with recurrent bacterial infections. J Exp Med 198:521–531
Moore CE, Segal S, Berendt AR, Hill AV, Day NP (2004) Lack of association between Toll-like receptor 2 polymorphisms and susceptibility to severe disease caused by Staphylococcus aureus. Clin Diagn Lab Immunol 11:1194–1197
Ogus AC, Yoldas B, Ozdemir T, Uguz A, Olcen S, Keser I, Coskun M, Cilli A, Yegin O (2004) The Arg753Gln polymorphism of the human toll-like receptor 2 gene in tuberculosis disease. Eur Respir J 23:219–223
Picard C, Puel A, Bonnet M, Ku CL, Bustamente J, Yang K, Soudais C, Dupuis S, Feinberg J, Fieschi C, Elbim C, Hitchcock R, Lammas D, Davies G, Al-Ghoanium A, Al-Reyes H, Al-Jumaah S, Al-Haijar S, Al-Mohsen IZ, Frayha HH, Rucker R, Hawn TR, Aderem A, Tufenkeji H, Haraguchi S, Day NK, Good RA, Gougerot-Pocidelo MA, Ozinsky A, Casanova JL (2003) Pyogenic bacterial infections in humans with IRAK-4 deficiency. Science 299: 2076–2079
Schroder JP, Kuhlmann WD (1992) Preventive tetanus immunization and avoidance of side effects of booster immunization (in German). Dtsch Med Wochenschr 117:1903–1906
Schroder NW, Schumann RR (2005) Single nucleotide polymorphisms of toll-like receptors and susceptibility to infectious diseases. Lancet Infect Dis 5:156–164
Schröder NW, Herman C, Hamann L, Göbel UB, Hartung T, Schuman RR (2003) High frequency of polymorphism Arg753Gln of the toll-like receptor 2 gene detected by a novel allele-specific PCR. J Mol Med 81:368–372
Seitz M (2003) Toll-like receptors: sensors of the innate immune system. Allergy 58:1247–1249
Sha Q, Truong-Tran AiQ, Plitt JR, Beck LA, Schleimer RP (2004) Activation of airway epithelial cells by toll-like receptor agonists. Am J Respir Cell Mol Biol 31:358–364
Tal G, Mandelberg A, Dalal I, Cesar K, Somekh E, Tal A, Oron A, Itskovich S, Ballin A, Houri S, Beigelman A, Lider O, Rechavi G, Amariglio N (2004). Association between common Toll-like receptor 4 mutations and severe respiratory syncytial virus disease. J Infect Dis 189:2057–2063
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Kutukculer, N., Yeniay, B.S., Aksu, G. et al. Arg753Gln Polymorphism of the Human Toll-like Receptor-2 Gene in Children with Recurrent Febrile Infections. Biochem Genet 45, 507–514 (2007). https://doi.org/10.1007/s10528-007-9091-0
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DOI: https://doi.org/10.1007/s10528-007-9091-0