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Volume 41 Issue 11
Nov.  2014
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Article Contents

Immunity Genes and Susceptibility to Otitis Media: A Comprehensive Review

doi: 10.1016/j.jgg.2014.10.003
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  • Corresponding author: E-mail address: xliu@med.miami.edu (Xue-Zhong Liu)
  • Received Date: 2014-08-15
  • Accepted Date: 2014-10-24
  • Rev Recd Date: 2014-10-23
  • Available Online: 2014-10-31
  • Publish Date: 2014-11-20
  • Otitis media (OM) is a middle ear infection associated with inflammation and pain. This disease frequently afflicts humans and is the major cause of hearing loss worldwide. OM continues to be one of the most challenging diseases in the medical field due to its diverse host targets and wide range of clinical manifestations. Substantial morbidity associated with OM is further exacerbated by high frequency of recurrent infections leading to chronic suppurative otitis media (CSOM). Children have greater susceptibility to, and thus, suffer most frequently from OM, which can cause significant deterioration in quality of life. Genetic factors have been demonstrated, in large part by twin and family studies, to be key determinants of OM susceptibility. In this review, we summarize the current knowledge on immunity genes and selected variants that have been associated with predisposition to OM. In particular, polymorphisms in innate immunity and cytokine genes have been strongly linked with the risk of developing OM. Future studies employing state-of-the-art technologies, including next-generation sequencing (NGS), will aid in the identification of novel genes associated with susceptibility to OM. This, in turn, will open up avenues for identifying high-risk individuals and designing novel therapeutic strategies based on precise targeting of these genes.
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  • [1]
    Acuin, J. Chronic suppurative otitis media Clin. Evid., 12 (2004),pp. 710-729
    [2]
    Ahmed, S., Shapiro, N.L., Bhattacharyya, N. Incremental health care utilization and costs for acute otitis media in children Laryngoscope, 124 (2014),pp. 301-305
    [3]
    Akira, S., Kishimoto, T. Role of interleukin-6 in macrophage function Curr. Opin. Hematol., 3 (1996),pp. 87-93
    [4]
    Alliprantis, A.O., Yang, R.B., Mark, M.R. et al. Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2 Science, 285 (1999),pp. 736-739
    [5]
    Alper, C.M., Winther, B., Hendley, J.O. et al. Cytokine polymorphisms predict the frequency of otitis media as a complication of rhinovirus and RSV infections in children Eur. Arch. Otorhinolaryngol., 226 (2009),pp. 199-205
    [6]
    Anggraeni, R., Hartanto, W.W., Djelantik, B. et al. Otitis media in Indonesian urban and rural school children Pediatr. Infect. Dis. J., 33 (2014),pp. 1010-1015
    [7]
    Arbour, N.C., Lorenz, E., Schutte, B.C. et al. Nat. Genet., 25 (2000),pp. 187-191
    [8]
    Baldini, M., Lohman, I.C., Halonen, R.P. et al. Am. J. Respir. Cell. Mol. Biol., 20 (1999),pp. 976-983
    [9]
    Barber, C., Ille, S., Vergison, A. et al. Acute otitis media in young children – what do parents say? Int. J. Pediatr. Otorhinolaryngol., 78 (2013),pp. 300-306
    [10]
    Barton, B.E. The biological effects of interleukin-6 Med. Res. Rev., 16 (1996),p. 87
    [11]
    Beutler, B. Inferences, questions and possibilities in TLR signaling Nature, 430 (2004),pp. 257-263
    [12]
    Boldt, A.B., Petzl-Erler, M.L. A new strategy for mannose-binding lectin gene haplotyping Hum. Mutat., 19 (2002),pp. 296-306
    [13]
    Carroll, S.R., Zald, P.B., Soler, Z.M. et al. Innate immunity gene single nucleotide polymorphisms and otitis media Int. J. Pediatr. Otorhinolaryngol., 76 (2012),pp. 976-979
    [14]
    Casselbrant, M.
    [15]
    Casselbrant, M.L., Mandel, E.M., Fall, P.A. et al. The heritability of otitis media: a twin and triplet study JAMA, 282 (1999),pp. 2125-2130
    [16]
    Cedzynski, M., Szemraj, J., Swierzko, A.S. et al. Mannan-binding lectin insufficiency in children with recurrent infections of the respiratory system Clin. Exp. Immunol., 136 (2004),pp. 304-311
    [17]
    Cleveland, M.G., Gorham, J.D., Murphy, T.L. et al. Lipoteichoic acid preparations of gram-positive bacteria induce interleukin-12 through a CD14-dependent pathway Infect. Immun., 64 (1996),pp. 1906-1912
    [18]
    Commins, S., Borish, L., Steinke, J.W. Immunologic messenger molecules: cytokines, interferons, and chemokines J. Allergy Clin. Immunol., 125 (2010),pp. S53-S72
    [19]
    Crossdale, D.J., Ollier, W.E., Thomson, W. et al. Mannose binding lectin (MBL) genotype distributions with relation to serum levels in UK Caucasoids Eur. J. Immunogenetics, 27 (2000),pp. 111-117
    [20]
    da Costa, S.S., Rosito, L.P., Dornelles, C. Sensorineural hearing loss in patients with chronic otitis media Eur. Arch. Otorhinolaryngol., 266 (2009),pp. 221-224
    [21]
    Dekker, J., Rossen, J.W., Büller, H.A. et al. The MUC family: an obituary Trends Biochem. Sci., 27 (2002),pp. 126-131
    [22]
    den Dunnen, J.T., Antonarakis, S.E. Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion Hum. Mutat., 15 (2000),pp. 7-12
    [23]
    Dobrovolskaia, M.A., Vogel, S.N. Toll receptors, CD14, and macrophage activation and deactivation by LPS Microbes Infect., 4 (2002),pp. 903-914
    [24]
    Dube, E., De Wals, P., Gilca, V. et al. Burden of acute otitis media on Canadian families Can. Fam. Physician, 57 (2011),pp. 60-65
    [25]
    Eder, W., Klimecki, W., Yu, L. et al. Toll-like receptor 2 as a major gene for asthma in children of European farmers J. Allergy Clin. Immunol., 113 (2004),pp. 482-488
    [26]
    Eggleton, P., Reid, K.B.M. Lung surfactant proteins involved in innate immunity Curr. Opin. Immunol., 11 (1999),pp. 28-33
    [27]
    Elsheikh, M.N., Mahfouz, M.E. Laryngoscope, 116 (2006),pp. 365-369
    [28]
    Emonts, M., Veenhoven, R.H., Wiertsema, S.P. et al. Pediatrics, 120 (2007),pp. 814-823
    [29]
    Emonts, M., Wiertsema, S.P., Veenhoven, R.H. et al. The 4G/4G plasminogen activator inhibitor-1 genotype is associated with frequent recurrence of acute otitis media Pediatrics, 120 (2007),pp. e317-323
    [30]
    Farrar, M.A., Schreiber, R.D. The molecular cell biology of interferon-gamma and its receptor Annu. Rev. Immunol., 11 (1993),pp. 571-611
    [31]
    Floros, J., DiAngelo, S., Koptides, M. et al. Human SP-A locus: allele frequencies and linkage disequilibrium between the two surfactant protein A genes Am. J. Respir. Cell Mol. Biol., 15 (1996),pp. 489-498
    [32]
    Gentile, D.A., Doyle, W.J., Zeevi, A. et al. Cytokine gene polymorphisms moderate illness severity in infants with respiratory syncytial virus infection Hum. Immunol., 64 (2003),pp. 338-344
    [33]
    Greenberg, D., Bilenko, N., Liss, Z. et al. The burden of acute otitis media on the patient and the family Eur. J. Pediatr., 162 (2003),pp. 576-581
    [34]
    Grindler, D.J., Blank, S.J., Schulz, K.A. et al. Impact of otitis media severity on children's quality of life Otolaryngol. Head Neck Surg., 151 (2014),pp. 333-340
    [35]
    Gupta, D., Kirkland, T.N., Viriyakosol, S. et al. CD14 is a cell-activating receptor for bacterial peptidoglycan J. Biol. Chem., 271 (1996),pp. 23310-23316
    [36]
    Hafren, L., Kental, E., Einarsdottir, E. et al. Current knowledge of the genetics of otitis media Curr. Allergy Asthma Rep., 12 (2012),pp. 582-589
    [37]
    Hardisty-Hughes, R.E., Tateossian, H., Morse, S.A. et al. Hum. Mol. Genet., 15 (2006),pp. 3273-3279
    [38]
    Heikkinen, T. The role of respiratory viruses in otitis media Vaccine, 19 (2000),pp. S51-S55
    [39]
    Hirano, T., Kodama, S., Fujita, K. et al. Role of toll-like receptor 4 in innate immune responses in a mouse model of acute otitis media FEMS Immunol. Med. Microbiol., 49 (2007),pp. 75-83
    [40]
    Ilia, S., Goulielmos, G., Samonis, G. et al. Pediatr. Infect. Dis. J., 33 (2014),pp. 518-521
    [41]
    Jack, D.L., Turner, M.W. Anti-microbial activities of mannose-binding lectin Biochem. Soc. Trans., 31 (2003),pp. 753-757
    [42]
    , Medzhitov, R. Innate immune recognition Annu. Rev. Immunol., 20 (2002),pp. 197-216
    [43]
    Jensen, R.G., Koch, A., Homøe, P. The risk of hearing loss in a population with a high prevalence of chronic suppurative otitis media Int. J. Pediatr. Otorhinolaryngol., 77 (2013),pp. 1530-1535
    [44]
    Jin, J., Cardozo, T., Lovering, R.C. et al. Systematic analysis and nomenclature of mammalian F-box proteins Genes Dev., 18 (2004),pp. 2573-2580
    [45]
    Joki-Erkkila, V.P., Puhakka, H., Hurme, M. Cytokine gene polymorphism in recurrent acute otitis media Arch. Otolaryngol. Head Neck Surg., 128 (2002),pp. 17-20
    [46]
    Jonckheere, N., Skrypek, N., Frénois, F. et al. Membrane-bound mucin modular domains: from structure to function Biochimie, 95 (2013),pp. 1077-1086
    [47]
    Kang, T.L., Lee, S.B., Chae, G.T. A polymorphism in the toll-like receptor 2 is associated with IL-12 production from monocyte in lepromatous leprosy Cytokine, 20 (2002),pp. 56-62
    [48]
    Kerschner, J.E., Tripathi, S., Khampang, P. et al. MUC5AC expression in human middle ear epithelium of patients with otitis media Arch. Otolaryngol. Head Neck Surg., 136 (2010),pp. 819-824
    [49]
    Kim, J.I., Lee, C.J., Jin, M.S. et al. Crystal structure of CD14 and its implications for lipopolysaccharide signaling J. Biol. Chem., 280 (2005),pp. 11347-11351
    [50]
    Kipreos, E.T., Pagano, M. The F-box protein family Genome Biol., 1 (2000)
    [51]
    Kolo, E.S., Salisu, A.D., Yaro, A.M. et al. Sensorineural hearing loss in patients with chronic suppurative otitis media Indian J. Otolaryngol. Head Neck Surg., 64 (2012),pp. 59-62
    [52]
    Kral, A., O'Donoghue, G.M. Profound deafness in childhood N. Engl. J. Med., 363 (2010),pp. 1438-1450
    [53]
    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., 25 (2000),pp. 187-191
    [54]
    Kvestad, E., Kvaerner, K.J., Roysamb, E. et al. Otitis media: genetic factors and sex differences Twin Res., 7 (2004),pp. 239-244
    [55]
    Lachheb, J., Dhifallah, I.B., Chelbi, H. et al. Toll-like receptors and CD14 genes polymorphisms and susceptibility to asthma in Tunisian children Tissue Antigens, 71 (2008),pp. 417-425
    [56]
    Lahti, M., Löfgren, J., Martila, R. et al. Surfactant protein D gene polymorphism associated with severe respiratory syncytial virus infection Pediatr. Res., 51 (2002),pp. 696-699
    [57]
    Lee, H.Y., Andalibi, A., Webster, P. et al. BMC Infect. Dis., 4 (2004),p. 12
    [58]
    Lee, H.Y., Kim, Y., Lee, J.W. et al. Decreased expression of TLR-9 and cytokines in the presence of bacteria in patients with otitis media with effusion Clin. Exp. Otorhinolaryngol., 6 (2013),pp. 195-200
    [59]
    Lee, Y.C., Kim, C., Shim, J.S. et al. Toll-like receptors 2 and 4 and their mutations in patients with otitis media and middle ear effusion Clin. Exp. Otolaryngol., 1 (2008),pp. 189-195
    [60]
    Leichtle, A., Hernandez, M., Lee, J. et al. The role of DNA sensing and innate immune receptor TLR9 in otitis media Innate Immun., 18 (2012),pp. 3-13
    [61]
    Leichtle, A., Hernandez, M., Pak, K. et al. The toll-like receptor adaptor TRIF contributes to otitis media pathogenesis and recovery BMC Immunol., 10 (2009),p. 45
    [62]
    Leichtle, A., Hernandez, M., Pak, K. et al. TLR4-mediated induction of TLR2 signaling is critical in the pathogenesis and resolution of otitis media Innate Immun., 15 (2009),pp. 205-215
    [63]
    Leichtle, A., Lai, Y., Wollenberg, B. et al. Innate signaling in otitis media: pathogenesis and recovery Curr. Allergy Asthma Rep., 11 (2011),pp. 78-84
    [64]
    Leth-Larsen, R., Garred, P., Jensenius, H. et al. J. Immunol., 174 (2005),pp. 1532-1538
    [65]
    Li, J.D., Hermansson, A., Ryan, A.F. et al. Panel 4: recent advances in otitis media in molecular biology, biochemistry, genetics, and animal models Otolaryngol. Head Neck Surg., 148 (2013),pp. E52-E63
    [66]
    Lipscombe, R.J., Sumiya, M., Summerfield, J.A. et al. Distinct physicochemical characteristics of human mannose binding protein expressed by individual of differing genotype J. Immunol., 85 (1995),pp. 660-667
    [67]
    Löfgren, J., Marrtila, R., Renko, M. et al. Toll-like receptor 4 Asp299Gly polymorphism in respiratory syncytial virus epidemics Pediatr. Pulmonol., 45 (2010),pp. 687-692
    [68]
    Lorenz, E., Hallman, M., Marttila, R. et al. Association between the Asp299Gly polymorphism in the toll-like receptor 4 and premature births in the Finnish population Pediatr. Res., 52 (2002),pp. 373-376
    [69]
    Lorenz, E., Mira, J.P., Cornish, K.L. et al. A novel polymorphism in the toll-like receptor 2 gene and its potential association with staphylococcal infection Infect. Immun., 68 (2000),pp. 6398-6401
    [70]
    Madsen, H.O., Garred, P., Kurtzhals, J.A. et al. A new frequent allele is the missing link in the structural polymorphism of the human mannan-binding protein Immunogenetics, 40 (1994),pp. 37-44
    [71]
    Madsen, H.O., Garred, P., Thiel, S. et al. Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein J. Immunol., 155 (1995),pp. 3013-3020
    [72]
    Madsen, H.O., Satz, M.L., Hogh, B. et al. Different molecular events result in low protein levels of mannan-binding lectin in populations from southeast Africa and South America J. Immunol., 161 (1998),pp. 3169-3175
    [73]
    Malley, R., Henneke, P., Morse, S.C. et al. Recognition of pneumolysin by toll-like receptor 4 confers resistance to pneumococcal infection Proc. Natl. Acad. Sci. USA, 100 (2003),pp. 1966-1971
    [74]
    McCormick, D.P., Grady, J.J., Diego, A. et al. Acute otitis media severity: association with cytokine gene polymorphisms and other risk factors Int. J. Pediatr. Otorhinolaryngol., 75 (2011),pp. 708-712
    [75]
    Medzithov, R., Preston-Hurlburt, P., A human homologue of the drosophila toll protein signals activation of adaptive immunity Nature, 388 (1997),pp. 394-397
    [76]
    Melhuish, T.A., Wotton, D. The interaction of the carboxyl terminus-binding protein with the Smad corepressor TGIF is disrupted by a holoprosencephaly mutation in TGIF J. Biol. Chem., 275 (2000),pp. 39762-39766
    [77]
    Mohr, P.E., Feldman, J.J., Dunbar, J.L. et al. The societal costs of severe to profound hearing loss in the United States Int. J. Technol. Assess. Health Care, 16 (2000),pp. 1120-1135
    [78]
    Monasta, L., Ronfani, L., Marchetti, F. et al. Burden of disease caused by otitis media: systematic review and global estimates PLoS ONE, 7 (2012),p. e36226
    [79]
    Nokso-Koivisto, J., Chonmaitree, T., Jennings, K. et al. Polymorphisms of immunity genes and susceptibility to otitis media in children PLoS ONE, 9 (2014),p. e93930
    [80]
    Novak, N., Yu, C.F., Bussmann, C. et al. Putative association of a TLR9 promoter polymorphism with atopic eczema Allergy, 62 (2007),pp. 766-772
    [81]
    Nuytinck, L., De Meester, E., Van Thielen, M. et al. Role of mannose-binding lectin (MBL2) genotyping in predicting the risk of recurrent otitis media (rOM) Adv. Exp. Med. Biol., 586 (2006),pp. 281-290
    [82]
    Olatoke, F., Ologe, F.E., Nwawolo, C.C. et al. The prevalence of hearing loss among school children with chronic suppurative otitis media in Nigeria, and its effect on academic performance Ear Nose Throat J., 87 (2008),p. E19
    [83]
    Orji, F. A survey of the burden of management of chronic suppurative otitis media in a developing country Ann. Med. Health Sci. Res., 3 (2013),pp. 598-601
    [84]
    Paananen, R., Glumoff, V., Hallman, M. Surfactant protein A and D expression in the porcine Eustachian tube FEBS Lett., 452 (1999),pp. 141-144
    [85]
    Papp, Z., Rezes, S., Jokay, I. et al. Sensorineural hearing loss in chronic otitis media Otol. Neurotol., 24 (2003),pp. 141-144
    [86]
    Patel, A., Gentile, D.A., Koehrsen, J. et al. Association between TGF-β1 genotype and the development of otitis media (OM) in young children during respiratory virus season J. Allergy Clin. Immunol., 117 (2006),p. S318
    [87]
    Patel, J.A., Nair, S., Revai, K. et al. Association of proinflammatory cytokine gene polymorphisms with susceptibility to otitis media J. Pediatr., 118 (2006),pp. 2273-2279
    [88]
    Pettigrew, M.M., Gent, J.F., Zhu, Y. et al. Association of surfactant protein A polymorphisms with otitis media in infants at risk of asthma BMC Med. Genet., 7 (2006),p. 68
    [89]
    Pichichero, M.E. Otitis media Pediatr. Clin. North Am., 60 (2013),pp. 391-407
    [90]
    Preciado, D., Goyal, S., Rahimi, M. et al. MUC5B is the predominant mucin glycoprotein in chronic otitis media fluid Pediatr. Res., 68 (2010),pp. 231-236
    [91]
    Qureishi, A., Lee, Y., Belfield, K. et al. Update on otitis media – prevention and treatment Infect. Drug Resist., 7 (2014),pp. 15-24
    [92]
    Rämet, M., Löfgren, J., Alho, O.P. et al. Surfactant protein-A gene locus associated with recurrent otitis media J. Pediatr., 138 (2001),pp. 266-268
    [93]
    Revai, K., Patel, J.A., Grady, J.J. et al. Association between cytokine gene polymorphisms and risk for upper respiratory tract infection and acute otitis media Clin. Infect. Dis., 49 (2009),pp. 257-261
    [94]
    Rovers, M., Haggard, M., Gannon, M. et al. Heritability of symptom domains in otitis media: a longitudinal study of 1373 twin pairs Am. J. Epidemiol., 155 (2002),pp. 958-964
    [95]
    Rovers, M.M., Schilder, A.G., Zielhuis, G.A. et al. Otitis media Lancet, 363 (2004),pp. 465-473
    [96]
    Rye, M.S., Wiertsema, S.P., Scaman, E.S. et al. FBXO11, a regulator of the TGFbeta pathway, is associated with severe otitis media in Western Australian children Genes Immun., 12 (2011),pp. 352-359
    [97]
    Sale, M.M., Chen, W.M., Weeks, D.E. et al. Evaluation of 15 functional candidate genes for association with chronic otitis media with effusion and/or recurrent otitis media (COME/ROM) PLoS ONE, 6 (2011),p. e22297
    [98]
    Schmuczerova, J., Brdicka, R., Dostal, M. et al. Genetic variability of HVRII mtDNA in cord blood and respiratory morbidity in children Mutat. Res., 666 (2009),pp. 1-7
    [99]
    Segade, F., Daly, K.A., Allred, D. et al. Arch. Otolaryngol. Head Neck Surg., 132 (2006),pp. 729-733
    [100]
    Seo, S.R., Lallemand, F., Ferrand, N. et al. The novel E3 ubiquitin ligase Tiul1 associates with TGIF to target Smad2 for degradation EMBO J., 23 (2004),pp. 3780-3792
    [101]
    Sims, J.E., March, C.J., Cosman, D. et al. cDNA expression cloning of the IL-1 receptor, a member of the immunoglobulin superfamily Science, 249 (1988),pp. 585-589
    [102]
    Steffensen, R., Thiel, S., Varming, K. et al. J. Immunol. Methods, 241 (2000),pp. 33-42
    [103]
    Sullivan, K.M., Wooten, C., Goldman, D. et al. Mannose-binding protein genetic polymorphisms in black patients with systemic lupus erythematosus Arthritis Rheum., 39 (1996),pp. 2046-2051
    [104]
    Sumiya, M., Super, M., Tabona, P. et al. Molecular basis of opsonic defect in immunodeficient children Lancet, 337 (1991),pp. 1569-1570
    [105]
    Sun, J., Sun, J. Intracranial complications of chronic otitis media Eur. Arch. Otorhinolaryngol. (2014)
    [106]
    Taanman, J.W. The mitochondrial genome: structure, transcription, translation and replication Biochem. Biophys. Acta, 1410 (1999),pp. 103-123
    [107]
    Takeuchi, O., Hoshino, K., Kawai, T. et al. Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components Immunity, 11 (1999),pp. 443-451
    [108]
    Tal, G., Mandelberg, A., Dalal, I. et al. Association between common toll-like receptor 4 mutations and severe respiratory syncytial virus disease J. Infect. Dis., 189 (2004),pp. 2057-2063
    [109]
    Tateossian, H., Morse, S., Parker, A. et al. Otitis media in the TGIF knockout mouse implicates TGF-β signaling in chronic middle ear inflammatory disease Hum. Mol. Genet., 22 (2013),pp. 2553-2565
    [110]
    Teele, D.W., Klein, J.O., Rosner, B. Epidemiology of otitis media during the first seven years of life in children in greater Boston: a prospective, cohort study J. Infect. Dis., 160 (1989),pp. 83-94
    [111]
    Tracey, K.J., Cerami, A. Tumor necrosis factor: a pleiotropic cytokine and therapeutic target Annu. Rev. Med., 45 (1994),pp. 491-503
    [112]
    Trzpis, K., Kasprzycka, E., Skotnicka, B. et al. Expression of toll-like receptors on peripheral white blood cells in acute otitis media Otololaryngol. Pol., 68 (2014),pp. 77-82
    [113]
    Turner, M.W. Deficiency of mannan binding protein: a new complement deficiency syndrome Clin. Exp. Immunol., 86 (1991),pp. 53-56
    [114]
    Ubell, M., Kerschner, J.E., Wackym, A. et al. MUC2 expression in human middle ear epithelium of patients with otitis media Arch. Otolaryngol. Head Neck Surg., 134 (2008),pp. 1-6
    [115]
    Ubell, M.L., Khampang, P., Kerschner, J.E. Laryngoscope, 120 (2010),pp. 132-138
    [116]
    Vuononvirta, J., Peltola, V., Mertsola, J. et al. Pediatr. Infect. Dis. J., 32 (2013),pp. 1185-1188
    [117]
    Vuononvirta, J., Toivonen, L., Grondahl-Yli-Hannuksela, K. et al. Nasopharyngeal bacterial colonization and gene polymorphisms of mannose-binding-lectin and toll-like receptors 2 and 4 in infants PLoS ONE, 6 (2011),p. e26198
    [118]
    Wiertsema, S.P., Khoo, S.K., Baynam, G. et al. Association of CD14 promoter polymorphism with otitis media and pneumococcal vaccine responses Clin. Vaccine Immunol., 13 (2006),pp. 892-897
    [119]
    Wiertsema, S.P., Herpers, B.L., Veenhoven, R.H. et al. Functional polymorphism in the mannan-binding lectin 2 gene: effect on MBL levels and otitis media J. Allergy Clin. Immunol., 117 (2006),pp. 1344-1350
    [120]
    Wotton, D., Lo, R.S., Swaby, L.A. et al. Multiple modes of repression by the Smad transcriptional corepressor TGIF J. Biol. Chem., 274 (1999),pp. 37105-37110
    [121]
    Wright, S.D., Ramos, R.A., Tobias, P.S. et al. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein Science, 249 (1999),pp. 1431-1433
    [122]
    Yorgancılar, E., Yildirim, M., Gun, R. et al. Complications of chronic suppurative otitis media: a retrospective review Eur. Arch. Otorhinolaryngol., 270 (2013),pp. 69-76
    [123]
    Yüce, S., Polat, K., Onder, I. et al. Chronic otitis media with multiple complications J. Craniofac. Surg., 24 (2013),pp. e403-405
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