title: Association of cytokine gene polymorphisms and risk factors with otitis media proneness in children.
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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  • 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.
authors.affiliation: Center for medical genetic and immunology, Clinical Center of Montenegro, Str. Ljubljanska BB, 81 000, Podgorica, Montenegro. oliveram@ac.me.|Clinical Center of Montenegro, Medical Faculty, University of Montenegro, Podgorica, Montenegro. oliveram@ac.me.
authors.forename: Olivera
authors.initials: O
authors.lastname: Miljanović
authors.affiliation: Military Medical Academy, Institute of Medical Research, Belgrade, Serbia.
authors.forename: Bojana
authors.initials: B
authors.lastname: Cikota-Aleksić
authors.affiliation: Department for Anesthesiology, Department for Otorhinolaryngology, Clinical Center of Montenegro, Institute for Children Diseases, Podgorica, Montenegro.
authors.forename: Dragan
authors.initials: D
authors.lastname: Likić
authors.affiliation: Military Medical Academy, Institute of Medical Research, Belgrade, Serbia.
authors.forename: Danilo
authors.initials: D
authors.lastname: Vojvodić
authors.affiliation: Department for Anesthesiology, Department for Otorhinolaryngology, Clinical Center of Montenegro, Institute for Children Diseases, Podgorica, Montenegro.
authors.forename: Ognjen
authors.initials: O
authors.lastname: Jovićević
authors.affiliation: Military Medical Academy, Institute of Medical Research, Belgrade, Serbia.
authors.forename: Zvonko
authors.initials: Z
authors.lastname: Magić
mesh_terms: D017677:Age Distribution; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D007376:Interleukin-2 / Q000097:blood / Q000235:genetics*; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D010033:Otitis Media / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D007376:Interleukin-2; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: Cytokines; Gene polymorphisms; Otitis media; Otitis media proneness; Risk factors