Background: Streptococcus pneumoniae and Neisseria meningitidis are frequent pathogens in life-threatening infections.
Genetic variation in the immune system may predispose to these infections. Nuclear factor-κB is a key
component of the TLR-pathway, controlled by inhibitors, encoded by the genes NFKBIA, NFKBIE and NFKBIZ.
We aimed to replicate previous findings of genetic variation associated with invasive pneumococcal disease
(IPD), and to assess whether similar associations could be found in invasive meningococcal disease (IMD).
Methods: Caseswith IPD and IMD and controlswere identified by linking Danish national registries. DNAwas obtained
from the Danish Neonatal Screening Biobank. The association between SNPs and susceptibility to IPD and
IMD, mortality and pneumococcal serotypes was investigated.
Results: 372 childrenwith pneumococcalmeningitis, 907with pneumococcal bacteremia and 1273 controlswere
included.We included 406 cases with meningococcal meningitis, 272 with meningococcal bacteremia, and 672
controls.
The NFKBIE SNP was associated with increased risk of pneumococcal meningitis (aOR 1.68; 95% CI: 1.20–2.36),
but not bacteremia (aOR 1.08; 95% CI: 0.86–1.35). The remaining SNPs were not associated with susceptibility
to invasive disease. None of the SNPs were associated with risk of IMD or mortality.
Conclusions: A NFKBIE polymorphism was associated with increased risk of pneumococcal meningitis.