title: Mannose-Binding Lectin Gene, MBL2, Polymorphisms Do Not Increase Susceptibility to Invasive Meningococcal Disease in a Population of Danish Children.
abstract: Background.  Neisseria meningitidis is the cause of meningococcal bacteremia and meningitis, and nasopharyngeal colonization with this pathogen is common. The incidence of invasive disease is highest in infants, whereas adolescents more often are carriers. Altered regulation or dysfunction of the innate immune system may predispose to invasive meningococcal disease (IMD). In this study, we investigated the effect of genetic variation in the mannose-binding lectin gene, MBL2, and its promoter on susceptibility to IMD and IMD-associated mortality among children. Methods.  Children (<5 years) diagnosed during 1982-2007 with IMD and controls were identified through Danish national registries. DNA was obtained from the Danish Neonatal Screening Biobank. The associations between MBL2 diplotypes and IMD susceptibility and 30- and 90-day mortality were investigated using logistic regression analysis. Results.  We included 1351 children: 406 with meningitis, 272 with bacteremia, and 673 age- and sex-matched controls. Of the children studied, 1292 (96%) were successfully genotyped and assigned MBL2 diplotypes. The median age in IMD cases was 19.1 months (interquartile range [IQR], 8.8-32.2 months). Children with defective MBL2 diplotypes were not at higher risk for meningococcal meningitis than children with intermediate and normal diplotypes (odds ratio [OR] = 0.69; 95% confidence interval [CI], .47-1.02). Similar results were found for children with bacteremia and defective diplotypes (OR = 0.84; 95% CI, .53-1.32) as well as for all cases (OR = 0.75; 95% CI, .56-1.01). There was no association between MBL2 diplotypes and mortality. Conclusions.  Defective MBL2 diplotypes did not predict either an increased IMD susceptibility or mortality in a Danish population of children.
authors.affiliation: Department of Infectious Diseases ; Clinical Research Centre , Hvidovre Hospital ; Faculty of Health Sciences , University of Copenhagen.
authors.forename: Lene F
authors.initials: LF
authors.lastname: Lundbo
authors.affiliation: Department of Clinical Epidemiology , Aarhus University Hospital.
authors.forename: Henrik T
authors.initials: HT
authors.lastname: Sørensen
authors.affiliation: Department of Infectious Diseases.
authors.forename: Louise N
authors.initials: LN
authors.lastname: Clausen
authors.affiliation: Danish Centre for Neonatal Screening, Department for Congenital Disorders.
authors.forename: Mads V
authors.initials: MV
authors.lastname: Hollegaard
authors.affiliation: Danish Centre for Neonatal Screening, Department for Congenital Disorders.
authors.forename: David M
authors.initials: DM
authors.lastname: Hougaard
authors.affiliation: Division of Diagnostics and Infection Control.
authors.forename: Helle B
authors.initials: HB
authors.lastname: Konradsen
authors.affiliation: Department of Microbiological Surveillance and Research , Statens Serum Institut , Copenhagen ; Department for Pulmonary and Infectious Diseases , North Zealand Hospital Hillerød , Denmark.
authors.forename: Zitta Barrella
authors.initials: ZB
authors.lastname: Harboe
authors.affiliation: Department of Clinical Epidemiology , Aarhus University Hospital.
authors.forename: Mette
authors.initials: M
authors.lastname: Nørgaard
authors.affiliation: Department of Infectious Diseases ; Clinical Research Centre , Hvidovre Hospital ; Faculty of Health Sciences , University of Copenhagen.
authors.forename: Thomas
authors.initials: T
authors.lastname: Benfield
keywords: MBL deficiency; MBL2 genotypes; invasive meningococcal disease