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Association of cytokine gene polymorphisms and risk factors with otitis media proneness in children

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Abstract

In order to assess the association between gene polymorphisms and otitis media (OM) proneness, tumor necrosis factor alpha (TNFA) -308, interleukin (IL) 10-1082 and -3575, IL6 -597, IL2 -330, and CD14 -159 genotyping was performed in 58 OM-prone children and 85 controls who were exposed to similar number and frequency of environmental and host risk factors. The frequencies of genotypes (wild type vs. genotypes containing at least one polymorphic allele) were not significantly different between groups, except for IL10 -1082. Polymorphic genotypes IL10 -1082 GA and GG were more frequent in OM-prone children than in control group (RR 1.145, 95 % CI 1.011–1.298; p = 0.047). However, logistic regression did not confirm IL10 -1082 polymorphic genotypes as an independent risk factor for OM proneness.

Conclusion: The present study indicates that high-producing IL10 -1082 GA/GG genotypes may increase the risk for OM proneness in its carriers when exposed to other environmental/host risk factors (day care attendance, passive smoking, male sex, respiratory infections, and atopic manifestations). This study revealed no significant independent genetic association, but the lack of breastfeeding in infancy was found to be the only independent risk factor for development of OM-prone phenotype, implying that breastfeeding had a protective role in development of susceptibility to OM.

What is known:

• The pathogenesis of OM is of multifactorial nature, dependent on infection, environmental factors, and immune response of the child.

• Cytokines and CD14 play an important role in the presentation and clinical course of otitis media, but a clear link with otitis media proneness was not established.

What is new:

• This is the first clinical and genetic study on Montenegrin children with the otitis media-prone phenotype.

• The study revealed that high-producing IL10 -1082 genotypes may influence otitis media proneness in children exposed to other environmental/host risk factors.

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Abbreviations

CD14:

Cluster of differentiation 14

IL:

Interleukin

OM:

Otitis media

SNP:

Single nucleotide polymorphism

TNFA:

Tumor necrosis factor alpha

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Authors’ contributions

OM, DL, and OJ were involved in the clinical management of the patients and collection and analysis of data. BCA and ZM performed SNPs testing. DV took part in the interpretation of obtained results. All authors contributed in the preparation and revision of the manuscript.

Author information

Authors and Affiliations

  1. Center for medical genetic and immunology, Clinical Center of Montenegro, Str. Ljubljanska BB, 81 000, Podgorica, Montenegro

    Olivera Miljanović

  2. Military Medical Academy, Institute of Medical Research, Belgrade, Serbia

    Bojana Cikota-Aleksić, Danilo Vojvodić & Zvonko Magić

  3. Department for Anesthesiology, Department for Otorhinolaryngology, Clinical Center of Montenegro, Institute for Children Diseases, Podgorica, Montenegro

    Dragan Likić & Ognjen Jovićević

  4. Clinical Center of Montenegro, Medical Faculty, University of Montenegro, Podgorica, Montenegro

    Olivera Miljanović

Authors
  1. Olivera Miljanović
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  2. Bojana Cikota-Aleksić
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  3. Dragan Likić
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  4. Danilo Vojvodić
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  5. Ognjen Jovićević
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  6. Zvonko Magić
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Corresponding author

Correspondence to Olivera Miljanović.

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Funding

This study was approved and funded by the Ministry of Science of Montenegro (grant number: 01-404 from 7 June 2012) and the Ministry of Health of Montenegro (grant number: 01-2014 from 7 June 2012).

Conflict of interest

The authors declare that they have no conflict of interests.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committees and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from the parents of all children.

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Communicated by Peter de Winter

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Miljanović, O., Cikota-Aleksić, B., Likić, D. et al. Association of cytokine gene polymorphisms and risk factors with otitis media proneness in children. Eur J Pediatr 175, 809–815 (2016). https://doi.org/10.1007/s00431-016-2711-0

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  • DOI: https://doi.org/10.1007/s00431-016-2711-0

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