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Current Knowledge of the Genetics of Otitis Media

  • OTITIS (DP SKONER, SECTION EDITOR)
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Abstract

Otitis media is one of the most common childhood infections leading to doctor’s visits and a leading cause of antibiotic prescriptions in children. Twin and family studies have confirmed that the predisposition of developing a bacterial middle ear infection is genetically determined. Several case-control studies have been performed to analyze genes involved in inflammatory processes in search of potential associations. Modern genome-wide association approaches that require no prior assumptions of the involvement of a given gene locus in the risk of otitis media are currently being used to identify otitis media genes, and will hopefully give more detailed information on the pathogenesis of childhood otitis media. That information could be used in finding the high-risk patient, in the prevention of the disease, and in the design of new treatments.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Freid VM, Makuc DM, Rooks RN. Ambulatory health care visits by children: principal diagnosis and place of visit. Vital Health Stat. 1998;13(137):1–23.

    Google Scholar 

  2. Daly KA, Hoffman HJ, Kvaerner KJ, et al. Epidemiology, natural history, and risk factors: panel report from the Ninth International Research Conference on Otitis Media. Int J Pediatr Otorhinolaryngol. 2010;74:231–40.

    Article  PubMed  Google Scholar 

  3. Gonzales R, Malone DC, Maselli JH, et al. Excessive antibiotic use for acute respiratory infections in the United States. Clin Infect Dis. 2001;33:757–62.

    Article  PubMed  CAS  Google Scholar 

  4. Lubianca Neto JF, Hemb L, Silva DB. Systematic literature review of modifiable risk factors for recurrent acute otitis media in childhood. J Pediatr (Rio J). 2006;82:87–96.

    Article  Google Scholar 

  5. Paradise JL, Rockette HE, Colborn DK, et al. Otitis media in 2253 Pittsburgh-area infants: prevalence and risk factors during the first two years of life. Pediatrics. 1997;99:318–33.

    Article  PubMed  CAS  Google Scholar 

  6. Abrahams SW, Labbok MH. Breastfeeding and otitis media: a review of recent evidence. Curr Allergy Asthma Rep. 2011;11:508–12.

    Article  PubMed  Google Scholar 

  7. Bluestone CD. Pathogenesis of otitis media: role of eustachian tube. Pediatr Infect Dis J. 1996;15:281–91.

    Article  PubMed  CAS  Google Scholar 

  8. Daly KA, Rich SS, Levine S, et al. The family study of otitis media: design and disease and risk factor profiles. Genet Epidemiol. 1996;13:451–68.

    Article  PubMed  CAS  Google Scholar 

  9. Chantzi FM, Kafetzis DA, Bairamis T, et al. IgE sensitization, respiratory allergy symptoms, and heritability independently increase the risk of otitis media with effusion. Allergy. 2006;61:332–6.

    Article  PubMed  CAS  Google Scholar 

  10. Rovers MM, Schilder AG, Zielhuis GA, et al. Otitis media. Lancet. 2004;363:465–73.

    Article  PubMed  Google Scholar 

  11. Visscher PM, Hill WG, Wray NR. Heritability in the genomics era–concepts and misconceptions. Nat Rev Genet. 2008;9:255–66.

    Article  PubMed  CAS  Google Scholar 

  12. Kvaerner KJ, Tambs K, Harris JR, et al. Distribution and heritability of recurrent ear infections. Ann Otol Rhinol Laryngol. 1997;106:624–32.

    PubMed  CAS  Google Scholar 

  13. Casselbrant ML, Mandel EM, Fall PA, et al. The Heritability of Otitis Media: A Twin and Triplet Study. JAMA. 1999;282:2125–30.

    Article  PubMed  CAS  Google Scholar 

  14. Rovers M, Haggard M, Gannon M, et al. Heritability of symptom domains in otitis media: a longitudinal study of 1,373 twin pairs. Am J Epidemiol. 2002;155:958–64.

    Article  PubMed  Google Scholar 

  15. Casselbrant ML, Mandel EM, Rockette HE, et al. The genetic component of middle ear disease in the first 5 years of life. Archives of Otolaryngology -- Head & Neck Surgery. 2004;130:273–8.

    Article  Google Scholar 

  16. Kvestad E, Kvaerner KJ, Roysamb E, et al. Otitis media: genetic factors and sex differences. Twin Research. 2004;7:239–44.

    PubMed  Google Scholar 

  17. Almasy L, Blangero J. Multipoint Quantitative-Trait Linkage Analysis in General Pedigrees. Am J Human Genet. 1998;62:1198–211.

    Article  CAS  Google Scholar 

  18. • Hafren L, Kentala E, Jarvinen TM, et al. Genetic background and the risk of otitis media. Int J Pediatr Otorhinolaryngol 2011. The heritability of OM is estimated from pedigrees as opposed from twin studies.

  19. Dawn Teare M, Barrett JH. Genetic linkage studies. Lancet. 2005;366:1036–44.

    Article  PubMed  CAS  Google Scholar 

  20. Daly KA, Brown WM, Segade F, et al. Chronic and recurrent otitis media: a genome scan for susceptibility loci. Am J Hum Genet. 2004;75:988–97.

    Article  PubMed  CAS  Google Scholar 

  21. • Casselbrant ML, Mandel EM, Jung J, et al. Otitis media: a genome-wide linkage scan with evidence of susceptibility loci within the 17q12 and 10q22.3 regions. BMC Med Genet. 2009;10:85. A linkage study on a large cohort, with strict phenotype criteria.

    Article  PubMed  Google Scholar 

  22. Chen WM, Allen EK, Mychaleckyj JC, et al. Significant linkage at chromosome 19q for otitis media with effusion and/or recurrent otitis media (COME/ROM). BMC Med Genet. 2011;12:124.

    Article  PubMed  CAS  Google Scholar 

  23. Ruskamp JM, Hoekstra MO, Rovers MM, et al. Mannose-binding lectin and upper respiratory tract infections in children and adolescents: a review. Arch Otolaryngol Head Neck Surg. 2006;132:482–6.

    Article  PubMed  Google Scholar 

  24. Wiertsema SP, Herpers BL, Veenhoven RH, et al. Functional polymorphisms in the mannan-binding lectin 2 gene: effect on MBL levels and otitis media. J Allergy Clin Immunol. 2006;117:1344–50.

    Article  PubMed  CAS  Google Scholar 

  25. 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. 2006;586:281–90.

    Article  PubMed  CAS  Google Scholar 

  26. • Sale MM, Chen WM, Weeks DE, 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. 2011;6:e22297. This is a well designed candidate gene study on 15 genes. Initial findings in a large cohort are controlled in a separate cohort.

    Article  PubMed  CAS  Google Scholar 

  27. Leichtle A, Lai Y, Wollenberg B, et al. Innate signaling in otitis media: pathogenesis and recovery. Curr Allergy Asthma Rep. 2011;11:78–84.

    Article  PubMed  Google Scholar 

  28. Emonts M, Veenhoven RH, Wiertsema SP, et al. Genetic polymorphisms in immunoresponse genes TNFA, IL6, IL10, and TLR4 are associated with recurrent acute otitis media. Pediatrics. 2007;120:814–23.

    Article  PubMed  Google Scholar 

  29. Carroll SR, Zald PB, Soler ZM, et al. Innate immunity gene single nucleotide polymorphisms and otitis media. Int J Pediatr Otorhinolaryngol 2012.

  30. Lee YC, Kim C, Shim JS, et al. Toll-like receptors 2 and 4 and their mutations in patients with otitis media and middle ear effusion. Clin Exp Otorhinolaryngol. 2008;1:189–95.

    Article  PubMed  Google Scholar 

  31. Wiertsema SP, Khoo SK, Baynam G, et al. Association of CD14 promoter polymorphism with otitis media and pneumococcal vaccine responses. Clin Vaccine Immunol. 2006;13:892–7.

    Article  PubMed  CAS  Google Scholar 

  32. Wright JR. Immunoregulatory functions of surfactant proteins. Nat Rev Immunol. 2005;5:58–68.

    Article  PubMed  CAS  Google Scholar 

  33. Ramet M, Lofgren J, Alho OP, et al. Surfactant protein-A gene locus associated with recurrent otitis media. J Pediatr. 2001;138:266–8.

    Article  PubMed  CAS  Google Scholar 

  34. Pettigrew MM, Gent JF, Zhu Y, et al. Association of surfactant protein A polymorphisms with otitis media in infants at risk for asthma. BMC Med Genet. 2006;7:68.

    Article  PubMed  Google Scholar 

  35. Patel JA, Nair S, Revai K, et al. Association of proinflammatory cytokine gene polymorphisms with susceptibility to otitis media. Pediatrics. 2006;118:2273–9.

    Article  PubMed  Google Scholar 

  36. Revai K, Patel JA, Grady JJ, et al. Association between cytokine gene polymorphisms and risk for upper respiratory tract infection and acute otitis media. Clin Infect Dis. 2009;49:257–61.

    Article  PubMed  CAS  Google Scholar 

  37. Alper CM, Winther B, Hendley JO, et al. Cytokine polymorphisms predict the frequency of otitis media as a complication of rhinovirus and RSV infections in children. Eur Arch Otorhinolaryngol. 2009;266:199–205.

    Article  PubMed  Google Scholar 

  38. Gentile DA, Doyle WJ, Zeevi A, et al. Cytokine gene polymorphisms moderate illness severity in infants with respiratory syncytial virus infection. Hum Immunol. 2003;64:338–44.

    Article  PubMed  CAS  Google Scholar 

  39. Patel A, Gentile DA, Koehrsen J, et al. Association Between TGF-B1 Genotype and the Development of Otitis Media (OM) in Young Children during Respiratory Virus Season. J Allergy Clin Immunol. 2006;117:S318.

    Article  Google Scholar 

  40. McCormick DP, Grady JJ, Diego A, et al. Acute otitis media severity: Association with cytokine gene polymorphisms and other risk factors. Int J Pediatr Otorhinolaryngol 2011.

  41. Joki-Erkkila VP, Puhakka H, Hurme M. Cytokine gene polymorphism in recurrent acute otitis media. Arch Otolaryngol Head Neck Surg. 2002;128:17–20.

    PubMed  Google Scholar 

  42. Rye MS, Wiertsema SP, Scaman ES, et al. FBXO11, a regulator of the TGFbeta pathway, is associated with severe otitis media in Western Australian children. Genes Immun. 2011;12:352–9.

    Article  PubMed  CAS  Google Scholar 

  43. Segade F, Daly KA, Allred D, et al. Association of the FBXO11 gene with chronic otitis media with effusion and recurrent otitis media: the Minnesota COME/ROM Family Study. Arch Otolaryngol Head Neck Surg. 2006;132:729–33.

    Article  PubMed  Google Scholar 

  44. Bhutta F, Burton MJ, Goel A, et al. Susceptibility to chronoc otitis media with effusion is associated with polymorphism at the loci FBXO11 and SMAD2. Presented at the 11th International Congress of the European Society of Pediatric Otorhinolaryngology. Amsterdam, the Netherlands; May 20-23, 2012.

  45. Lin J, Tsuprun V, Kawano H, et al. Characterization of mucins in human middle ear and Eustachian tube. Am J Physiol Lung Cell Mol Physiol. 2001;280:L1157–67.

    PubMed  CAS  Google Scholar 

  46. Preciado D, Goyal S, Rahimi M, et al. MUC5B Is the predominant mucin glycoprotein in chronic otitis media fluid. Pediatr Res. 2010;68:231–6.

    Article  PubMed  CAS  Google Scholar 

  47. Ubell ML, Khampang P, Kerschner JE. Mucin gene polymorphisms in otitis media patients. Laryngoscope. 2010;120:132–8.

    Article  PubMed  CAS  Google Scholar 

  48. Mortensen EH, Lildholdt T, Gammelgard NP, et al. Distribution of ABO blood groups in secretory otitis media and cholesteatoma. Clin Otolaryngol Allied Sci. 1983;8:263–5.

    Article  PubMed  CAS  Google Scholar 

  49. Kalm O, Johnson U, Prellner K, et al. HLA frequency in patients with recurrent acute otitis media. Arch Otolaryngol Head Neck Surg. 1991;117:1296–9.

    Article  PubMed  CAS  Google Scholar 

  50. Kalm O, Johnson U, Prellner K. HLA frequency in patients with chronic secretory otitis media. Int J Pediatr Otorhinolaryngol. 1994;30:151–7.

    Article  PubMed  CAS  Google Scholar 

  51. Schmuczerova J, Brdicka R, Dostal M, et al. Genetic variability of HVRII mtDNA in cord blood and respiratory morbidity in children. Mutat Res. 2009;666:1–7.

    Article  PubMed  CAS  Google Scholar 

  52. Emonts M, Wiertsema SP, Veenhoven RH, et al. The 4 G/4G plasminogen activator inhibitor-1 genotype is associated with frequent recurrence of acute otitis media. Pediatrics. 2007;120:e317–23.

    Article  PubMed  Google Scholar 

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Acknowledgment

We thank David Adler, University of Washington, Department of Pathology, for the image of the human chromosomes.

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No potential conflicts of interest relevant to this article were reported.

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Authors and Affiliations

  1. Department of Otorhinolaryngology, Helsinki University Central Hospital, University of Helsinki, P.O. Box 220, 00029, HUS, Finland

    Lena Hafrén, Erna Kentala & Petri S. Mattila

  2. Department of Medical Genetics, Haartman Institute, University of Helsinki, P.O. Box 63, 00014, Helsinki, Finland

    Elisabet Einarsdottir & Juha Kere

  3. Research Program for Molecular Medicine, University of Helsinki, Helsinki, Finland

    Elisabet Einarsdottir

  4. Folkhälsan Institute of Genetics, Helsinki, Finland

    Juha Kere

  5. Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden

    Juha Kere

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  1. Lena Hafrén
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  2. Erna Kentala
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  3. Elisabet Einarsdottir
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  4. Juha Kere
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  5. Petri S. Mattila
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Correspondence to Lena Hafrén.

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Hafrén, L., Kentala, E., Einarsdottir, E. et al. Current Knowledge of the Genetics of Otitis Media. Curr Allergy Asthma Rep 12, 582–589 (2012). https://doi.org/10.1007/s11882-012-0292-1

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  • DOI: https://doi.org/10.1007/s11882-012-0292-1

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