title: Genetic susceptibility to invasive meningococcal disease: MBL2 structural polymorphisms revisited in a large case-control study and a systematic review.
abstract: Invasive infection caused by Neisseria meningitidis is a worldwide public health problem. Previous reports have indicated that carriage of common 'defective' structural polymorphisms of the host mannose-binding lectin gene (MBL2) greatly increases an individual's risk of developing the disease. We report the largest case-control study so far to investigate the effect of these polymorphisms in meningococcal disease (296 PCR-positive cases and 5196 population controls, all of European ancestry) and demonstrate that no change in risk is associated with the polymorphisms overall or in any age-defined subgroup. This finding contrasts with two smaller studies that reported an increase in risk. A systematic review of all studies of MBL2 polymorphisms in people of European ancestry published since 1999, including 24,693 individuals, revealed a population frequency of the combined 'defective'MBL2 allele of 0.230 (95% confidence limits: 0.226-0.234). The past reported associations of increased risk of meningococcal disease were because of low 'defective' allele frequencies in their study control populations (0.13 and 0.04) that indicate systematic problems with the studies. The data from our study and all other available evidence indicate that MBL2 structural polymorphisms do not predispose children or adults to invasive meningococcal disease.
authors.affiliation: Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK. dbradley09@qub.ac.uk
authors.forename: D T
authors.initials: DT
authors.lastname: Bradley
authors.forename: T W
authors.initials: TW
authors.lastname: Bourke
authors.forename: D J
authors.initials: DJ
authors.lastname: Fairley
authors.forename: R
authors.initials: R
authors.lastname: Borrow
authors.forename: M D
authors.initials: MD
authors.lastname: Shields
authors.forename: I S
authors.initials: IS
authors.lastname: Young
authors.forename: P F
authors.initials: PF
authors.lastname: Zipfel
authors.forename: A E
authors.initials: AE
authors.lastname: Hughes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016001:Confidence Intervals; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D060148:HapMap Project; D006801:Humans; D007223:Infant; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008589:Meningococcal Infections / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology; D008875:Middle Aged; D009345:Neisseria meningitidis / Q000472:pathogenicity; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D012307:Risk Factors; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin