title: Risk of repeated Moraxella catarrhalis colonization is increased in children with Toll-like receptor 4 Asp299Gly polymorphism.
abstract: BACKGROUND
  Moraxella catarrhalis is a common causative agent of acute otitis media and other respiratory infections in children. Toll-like receptor (TLR) 4 is an important protein of human innate immunity. One polymorphic site Asp299Gly of TLR4 is proven to result in an impaired response to lipopolysaccharide from Gram-negative bacteria. We investigated whether Finnish children who carry Asp299Gly had increased risk of M. catarrhalis colonization during their first 2 years of life.
  
  
  METHODS
  This was a prospective cohort study carried out in Turku, Finland. We studied M. catarrhalis colonization in 161 Finnish children, whose nasopharyngeal specimens were taken at 2, 12 and 24 months of age. The semiquantitative culture method was used for identification of different bacterial species and the pyrosequencing-based method for detection of TLR4 Asp299Gly.
  
  
  RESULTS
  Of 161 subjects, 126 (78%) were TLR4 A/A wild type and 35 (22%) were A/G heterozygote variants. The prevalence of M. catarrhalis increased from 24% at 2 months to 48% at 12 months and to 58% at 24 months of age. Of the 35 subjects with TLR4 variant, 15 (43%) were M. catarrhalis positive at all 3 time points, whereas only 11 (9%) subjects with TLR4 wild type were positive at these time points (relative risk 4.91, 95% confidence interval: 2.482-9.711, P=0.0001). Moreover, subjects with TLR4 variant had significantly higher bacterial load of M. catarrhalis in their nasopharynx than those with TLR4 wild type (P=0.0032).
  
  
  CONCLUSIONS
  Our results indicate that children with TLR4 Asp299Gly polymorphism have an increased risk of repeated M. catarrhalis colonization.
authors.affiliation: From the *Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare; †Department of Pediatric, Turku University Hospital; and ‡Turku Institute for Child and Youth Research, University of Turku, Turku, Finland.
authors.forename: Juho
authors.initials: J
authors.lastname: Vuononvirta
authors.forename: Ville
authors.initials: V
authors.lastname: Peltola
authors.forename: Jussi
authors.initials: J
authors.lastname: Mertsola
authors.forename: Qiushui
authors.initials: Q
authors.lastname: He
mesh_terms: D058491:Bacterial Load; D016009:Chi-Square Distribution; D002675:Child, Preschool; D005387:Finland; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D001936:Moraxella catarrhalis / Q000276:immunology / Q000302:isolation & purification*; D045828:Moraxellaceae Infections / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012008:Recurrence; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000276:immunology
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4