Association of variants of the gene for mannose-binding lectin with susceptibility to meningococcal disease. Meningococcal Research Group.
BACKGROUND
The reasons why meningococcal disease develops in only a small proportion of individuals carrying the causative bacteria are unknown. Differences in host responses to bacterial colonisation are thought to be involved, since people with deficiencies in the terminal components of the complement pathway, or of properdin, are susceptible to meningococcal disease. We postulate that genetic variants of mannose-binding lectin (MBL), a plasma opsonin that initiates another pathway of complement activation, might similarly cause susceptibility to meningococcal disease.


METHODS
The frequency of variants of the MBL gene was ascertained in children with meningococcal disease and controls from two independent studies; one hospital-based (194 patients and 272 controls [patients with non-infectious disorders]), and one community-based (72 patients and 110 controls [healthy individuals]), by means of PCR and restriction-enzyme digestion, with confirmation by DNA sequencing.


RESULTS
The proportion of people homozygous for MBL-variant alleles was higher in patients with meningococcal disease than in controls in the hospital study (15 [7.7%] vs four [1.5%]; odds ratio 6.5 [95% CI 2.0-27.2]) and in the community study (six [8.3%] vs three [2.7%]; 4.5 [0.9-29.1]). The population attributable fraction of cases attributable to MBL variants (homozygous and heterozygous) was 32%.


CONCLUSIONS
The MBL pathway is a critical determinant of meningococcal-disease susceptibility, and genetic variants of MBL might account for a third of all disease cases.
Hibberd
M L
ML
Department of Paediatrics, Imperial College School of Medicine at St Mary's, London, UK.
Sumiya
M
M
Summerfield
J A
JA
Booy
R
R
Levin
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D037222:Collectins; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007223:Infant; D037102:Lectins / Q000235:genetics; D008297:Male; D008589:Meningococcal Infections / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction
D002352:Carrier Proteins; D037222:Collectins; D037102:Lectins