title: Functional polymorphisms in the mannan-binding lectin 2 gene: effect on MBL levels and otitis media.
abstract: BACKGROUND
  Mannan-binding lectin (MBL) can bind to microorganisms, initiating the lectin pathway of complement activation. Aberrant MBL serum levels, caused by MBL2 gene polymorphisms, are a possible risk factor for recurrent infections. Within the 7 common MBL haplotypes, still considerable variation in MBL serum levels exists.
  
  
  OBJECTIVE
  To investigate functional MBL levels and MBL2 polymorphisms in a large cohort of children with recurrent acute otitis media.
  
  
  METHODS
  Twelve genetic variants in the MBL2 gene and functional MBL serum levels were determined in a cohort of children with recurrent acute otitis media. Haplotypes were constructed and associated with functional MBL serum levels and the number of otitis episodes in the previous year.
  
  
  RESULTS
  The 7 common MBL2 haplotypes mainly determine the level of functional MBL in serum. In addition, the 3130G>C single nucleotide polymorphism, located in exon 4, further significantly influenced functional MBL levels within the LXPA haplotype. LXPA carriers with 3130G showed a significantly lower geometric mean functional MBL serum level of 0.19 mug/mL compared with 0.70 mug/mL in 3130C carriers (P = .026). Nonwild-type MBL2 carriers between 12 and 24 months had a significantly increased number of otitis episodes (5.1/y) compared with wild-type MBL2 carriers (4.1/y; P = .027). In older children, this association was not found anymore.
  
  
  CONCLUSIONS
  Additional single nucleotide polymorphisms within the 7 common haplotypes can further explain the observed variation in functional MBL serum levels. MBL seems to be of particular clinical importance during early childhood, when maternally derived antibodies have waned, and protective adaptive immunity is not well developed yet.
  
  
  CONCLUSIONS
  Single nucleotide polymorphisms in the promoter region, in exon 1, and in exon 4 of MBL2 contribute to increased risk for otitis media in children younger than 2 years.
authors.affiliation: Department of Pediatric Immunology, University Medical Center Utrecht, The Netherlands.
authors.forename: Selma P
authors.initials: SP
authors.lastname: Wiertsema
authors.forename: Bjorn L
authors.initials: BL
authors.lastname: Herpers
authors.forename: Reinier H
authors.initials: RH
authors.lastname: Veenhoven
authors.forename: Marcel M M
authors.initials: MM
authors.lastname: Salimans
authors.forename: Henk J T
authors.initials: HJ
authors.lastname: Ruven
authors.forename: Elisabeth A M
authors.initials: EA
authors.lastname: Sanders
authors.forename: Ger T
authors.initials: GT
authors.lastname: Rijkers
mesh_terms: D000208:Acute Disease; D002648:Child; D002675:Child, Preschool; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D037601:Mannose-Binding Lectin / Q000097:blood / Q000235:genetics* / Q000502:physiology; D010033:Otitis Media / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D022242:Pneumococcal Vaccines / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D022242:Pneumococcal Vaccines