title: Polymorphisms of Mannose-binding Lectin and Toll-like Receptors 2, 3, 4, 7 and 8 and the Risk of Respiratory Infections and Acute Otitis Media in Children.
abstract: BACKGROUND
  Mannose-binding lectin (MBL) and toll-like receptors (TLRs) are important components of the innate immune system. We assessed the susceptibility of children with genetic variants in these factors to respiratory infections, rhinovirus infections and acute otitis media.
  
  
  METHODS
  In a prospective cohort study, blood samples from 381 Finnish children were analyzed for polymorphisms in MBL2 at codons 52, 54 and 57, TLR2 Arg753Gln, TLR3 Leu412Phe, TLR4 Asp299Gly, TLR7 Gln11Leu and TLR8 Leu651Leu. Children were followed up for respiratory infections until 24 months of age with daily diaries. Polymerase chain reaction and antigen tests were used for detection of respiratory viruses from nasal swabs.
  
  
  RESULTS
  Children with MBL variant genotype had a mean of 59 days with symptoms of respiratory infection per year, compared with 49 days in those with wild-type (P = 0.01). TLR8 polymorphisms were associated with an increased risk and TLR7 polymorphisms with a decreased risk of recurrent rhinovirus infections (P = 0.02 for both). TLR2 polymorphisms were associated with recurrent acute otitis media (P = 0.02). MBL polymorphisms were associated with an increased and TLR7 polymorphisms with a decreased risk of rhinovirus-associated acute otitis media (P = 0.03 and P = 0.006, respectively).
  
  
  CONCLUSIONS
  Genetic polymorphisms in MBL and TLRs promote susceptibility to or protection against respiratory infections. In addition to environmental factors, genetic variations may explain why some children are more prone to respiratory infections.
authors.affiliation: From the *Department of Pediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland; and †Turku Institute for Child and Youth Research, ‡Department of Medical Microbiology and Immunology, and §Department of Virology, University of Turku, Turku, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Toivonen
authors.forename: Juho
authors.initials: J
authors.lastname: Vuononvirta
authors.forename: Jussi
authors.initials: J
authors.lastname: Mertsola
authors.forename: Matti
authors.initials: M
authors.lastname: Waris
authors.forename: Qiushui
authors.initials: Q
authors.lastname: He
authors.forename: Ville
authors.initials: V
authors.lastname: Peltola
mesh_terms: D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics* / Q000276:immunology; D010033:Otitis Media / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012008:Recurrence; D012141:Respiratory Tract Infections / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000235:genetics* / Q000276:immunology; D051200:Toll-Like Receptor 8 / Q000235:genetics*
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; C495342:TLR2 protein, human; C495344:TLR3 protein, human; C495345:TLR4 protein, human; C495348:TLR7 protein, human; C495349:TLR8 protein, human; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8