title: MBL genotype and risk of invasive pneumococcal disease: a case-control study.
abstract: BACKGROUND
  Streptococcus pneumoniae is a major cause of morbidity and mortality in developed and developing countries. No common genetic determinants of susceptibility have been defined. Mannose-binding lectin (MBL) is a key mediator of innate host immunity that activates the complement pathway and directly opsonises some infectious pathogens. Mutations in three codons in the MBL gene have been identified, and individuals homozygous for a mutant genotype have very little or no serum MBL. We did a case-control study in the UK to assess whether these mutant genotypes were associated with invasive pneumococcal disease.
  
  
  METHODS
  The frequencies of genotypes defined by the three mutations in codons 52, 54, and 57, and a functional promoter polymorphism at -221, were compared in a two-stage study of 337 patients with invasive pneumococcal disease and 1032 controls. All individuals were recruited from an ethnically homogeneous white population in Oxfordshire, UK. Patients had S pneumoniae isolated from a normally sterile site.
  
  
  RESULTS
  In our initial set of participants, 28 (12%) of 229 patients and 18 (5%) of 353 controls were homozygotes for MBL codon variants (odds ratio 2.59 [95% CI 1.39-4.83], p=0.002). Neither heterozygosity for these codon variants nor the promoter polymorphism was associated with susceptibility. In a confirmatory study, 11 (10%) of 108 patients were MBL homozygotes compared with 36 (5%) of 679 controls (p=0.046).
  
  
  CONCLUSIONS
  Homozygotes for MBL codon variants, who represent about 5% of north Europeans and north Americans and larger proportions of populations in many developing countries, could be at substantially increased risk of invasive pneumococcal disease.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Suchismita
authors.initials: S
authors.lastname: Roy
authors.forename: Kyle
authors.initials: K
authors.lastname: Knox
authors.forename: Shelley
authors.initials: S
authors.lastname: Segal
authors.forename: David
authors.initials: D
authors.lastname: Griffiths
authors.forename: Catrin E
authors.initials: CE
authors.lastname: Moore
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Welsh
authors.forename: Alex
authors.initials: A
authors.lastname: Smarason
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Day
authors.forename: William L
authors.initials: WL
authors.lastname: McPheat
authors.forename: Derrick W
authors.initials: DW
authors.lastname: Crook
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003062:Codon; D037222:Collectins; D005260:Female; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011008:Pneumococcal Infections / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D018709:Statistics, Nonparametric; D013296:Streptococcus pneumoniae / Q000302:isolation & purification; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D002352:Carrier Proteins; D003062:Codon; D037222:Collectins