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Genetic Variation in NFKBIE Is Associated With Increased Risk of Pneumococcal Meningitis in Children

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Lundbo, Lene F ; Harboe, Zitta Barrella ; Clausen Nygaard, Louise ; Hollegaard, Mads V ; Sørensen, Henrik T ; Hougaard, David M ; Konradsen, Helle B ; Nørgaard, Mette ; Benfield, Thomas. / Genetic Variation in NFKBIE Is Associated With Increased Risk of Pneumococcal Meningitis in Children. I: EBioMedicine. 2016 ; Bind 3. s. 93-9.

Bibtex

@article{c4306a3c2ad046b6a6b89dc4e4353d6c,
title = "Genetic Variation in NFKBIE Is Associated With Increased Risk of Pneumococcal Meningitis in Children",
abstract = "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: Cases with IPD and IMD and controls were identified by linking Danish national registries. DNA was 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 children with pneumococcal meningitis, 907 with pneumococcal bacteremia and 1273 controls were 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.",
author = "Lundbo, {Lene F} and Harboe, {Zitta Barrella} and {Clausen Nygaard}, Louise and Hollegaard, {Mads V} and S{\o}rensen, {Henrik T} and Hougaard, {David M} and Konradsen, {Helle B} and Mette N{\o}rgaard and Thomas Benfield",
year = "2016",
month = jan,
doi = "10.1016/j.ebiom.2015.11.048",
language = "English",
volume = "3",
pages = "93--9",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - Genetic Variation in NFKBIE Is Associated With Increased Risk of Pneumococcal Meningitis in Children

AU - Lundbo, Lene F

AU - Harboe, Zitta Barrella

AU - Clausen Nygaard, Louise

AU - Hollegaard, Mads V

AU - Sørensen, Henrik T

AU - Hougaard, David M

AU - Konradsen, Helle B

AU - Nørgaard, Mette

AU - Benfield, Thomas

PY - 2016/1

Y1 - 2016/1

N2 - 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: Cases with IPD and IMD and controls were identified by linking Danish national registries. DNA was 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 children with pneumococcal meningitis, 907 with pneumococcal bacteremia and 1273 controls were 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.

AB - 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: Cases with IPD and IMD and controls were identified by linking Danish national registries. DNA was 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 children with pneumococcal meningitis, 907 with pneumococcal bacteremia and 1273 controls were 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.

U2 - 10.1016/j.ebiom.2015.11.048

DO - 10.1016/j.ebiom.2015.11.048

M3 - Journal article

C2 - 26870821

VL - 3

SP - 93

EP - 99

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

ER -

ID: 46224028