Mannose-binding lectin gene, MBL2, polymorphisms are not associated with susceptibility to invasive pneumococcal disease in children

Lene Fogt Lundbo; Zitta Barrella Harboe; Louise Nygaard Clausen; Mads Vilhelm Hollegaard; Henrik Toft Sørensen; David Michael Hougaard; Helle Bossen Konradsen; Mette Nørgaard; Thomas Benfield

doi:10.1093/cid/ciu276

Mannose-binding lectin gene, MBL2, polymorphisms are not associated with susceptibility to invasive pneumococcal disease in children

Lene Fogt Lundbo, Zitta Barrella Harboe, Louise Nygaard Clausen, Mads Vilhelm Hollegaard, Henrik Toft Sørensen, David Michael Hougaard, Helle Bossen Konradsen, Mette Nørgaard, Thomas Benfield

Department of Clinical Medicine

15 Citations (Scopus)

Abstract

Background. Most children are transiently colonized with Streptococcus pneumoniae, but very few develop invasive pneumococcal disease (IPD). Host genetic variation of innate immunity may predispose to IPD. We investigated the effect of genetic variation in the mannose-binding lectin gene, MBL2, on susceptibility and disease severity of IPD in previously healthy children aged <5 years. Methods. IPD cases were identified through national registries. DNA was obtained from the Danish Neonatal Screening Biobank. Pneumococcal serotypes were determined by Quellung reaction. The associations between MBL2 diplotypes and IPD susceptibility, serotypes, and outcome were investigated using logistic regression analysis. Results. We included 372 cases with meningitis, 907 with bacteremia, and 1263 age- and sex-matched controls; 2372 individuals were successfully genotyped and assigned MBL2 diplotypes. The median age in our combined case series was 13 months. Children with defective diplotypes were not at higher risk for meningitis than children with other diplotypes (odds ratio [OR], 0.85; 95% confidence interval [CI], .56-1.28). Similar results were found for bacteremia (OR, 0.89; 95% CI, .68-1.15) as well as for all cases (OR, 0.87; 95% CI, .70-1.09). There was no association with susceptibility to recurrent IPD (n = 12) for children with defective diplotypes compared with cases with a single episode (OR, 0.53; 95% CI, .07-4.13) and with all controls (OR, 0.46; 95% CI, .06-3.56). There was no association between diplotypes and mortality or between diplotypes and pneumococcal serotypes. Conclusions. Defective MBL2 polymorphisms did not predict increased IPD susceptibility in children born in Northern Europe.

Original language	English
Journal	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Volume	59
Issue number	4
Pages (from-to)	e66-e71
Number of pages	6
ISSN	1058-4838
DOIs	https://doi.org/10.1093/cid/ciu276
Publication status	Published - 15 Aug 2014

Keywords

Child, Preschool
Denmark
Disease Susceptibility
Female
Genetic Predisposition to Disease
Humans
Infant
Infant, Newborn
Male
Mannose-Binding Lectin
Pneumococcal Infections
Polymorphism, Genetic
Serogroup
Streptococcus pneumoniae

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10.1093/cid/ciu276

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Lundbo, L. F., Harboe, Z. B., Clausen, L. N., Hollegaard, M. V., Sørensen, H. T., Hougaard, D. M., Konradsen, H. B., Nørgaard, M., & Benfield, T. (2014). Mannose-binding lectin gene, MBL2, polymorphisms are not associated with susceptibility to invasive pneumococcal disease in children. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 59(4), e66-e71. https://doi.org/10.1093/cid/ciu276

Mannose-binding lectin gene, MBL2, polymorphisms are not associated with susceptibility to invasive pneumococcal disease in children. / Lundbo, Lene Fogt; Harboe, Zitta Barrella; Clausen, Louise Nygaard et al.

In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Vol. 59, No. 4, 15.08.2014, p. e66-e71.

Research output: Contribution to journal › Journal article › Research › peer-review

Lundbo, LF, Harboe, ZB, Clausen, LN, Hollegaard, MV, Sørensen, HT, Hougaard, DM, Konradsen, HB, Nørgaard, M & Benfield, T 2014, 'Mannose-binding lectin gene, MBL2, polymorphisms are not associated with susceptibility to invasive pneumococcal disease in children', Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, vol. 59, no. 4, pp. e66-e71. https://doi.org/10.1093/cid/ciu276

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title = "Mannose-binding lectin gene, MBL2, polymorphisms are not associated with susceptibility to invasive pneumococcal disease in children",

abstract = "Background. Most children are transiently colonized with Streptococcus pneumoniae, but very few develop invasive pneumococcal disease (IPD). Host genetic variation of innate immunity may predispose to IPD. We investigated the effect of genetic variation in the mannose-binding lectin gene, MBL2, on susceptibility and disease severity of IPD in previously healthy children aged <5 years. Methods. IPD cases were identified through national registries. DNA was obtained from the Danish Neonatal Screening Biobank. Pneumococcal serotypes were determined by Quellung reaction. The associations between MBL2 diplotypes and IPD susceptibility, serotypes, and outcome were investigated using logistic regression analysis. Results. We included 372 cases with meningitis, 907 with bacteremia, and 1263 age- and sex-matched controls; 2372 individuals were successfully genotyped and assigned MBL2 diplotypes. The median age in our combined case series was 13 months. Children with defective diplotypes were not at higher risk for meningitis than children with other diplotypes (odds ratio [OR], 0.85; 95% confidence interval [CI], .56-1.28). Similar results were found for bacteremia (OR, 0.89; 95% CI, .68-1.15) as well as for all cases (OR, 0.87; 95% CI, .70-1.09). There was no association with susceptibility to recurrent IPD (n = 12) for children with defective diplotypes compared with cases with a single episode (OR, 0.53; 95% CI, .07-4.13) and with all controls (OR, 0.46; 95% CI, .06-3.56). There was no association between diplotypes and mortality or between diplotypes and pneumococcal serotypes. Conclusions. Defective MBL2 polymorphisms did not predict increased IPD susceptibility in children born in Northern Europe.",

keywords = "Child, Preschool, Denmark, Disease Susceptibility, Female, Genetic Predisposition to Disease, Humans, Infant, Infant, Newborn, Male, Mannose-Binding Lectin, Pneumococcal Infections, Polymorphism, Genetic, Serogroup, Streptococcus pneumoniae",

author = "Lundbo, {Lene Fogt} and Harboe, {Zitta Barrella} and Clausen, {Louise Nygaard} and Hollegaard, {Mads Vilhelm} and S{\o}rensen, {Henrik Toft} and Hougaard, {David Michael} and Konradsen, {Helle Bossen} and Mette N{\o}rgaard and Thomas Benfield",

note = "{\textcopyright} The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].",

year = "2014",

month = aug,

day = "15",

doi = "10.1093/cid/ciu276",

language = "English",

volume = "59",

pages = "e66--e71",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "4",

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TY - JOUR

T1 - Mannose-binding lectin gene, MBL2, polymorphisms are not associated with susceptibility to invasive pneumococcal disease in children

AU - Lundbo, Lene Fogt

AU - Harboe, Zitta Barrella

AU - Clausen, Louise Nygaard

AU - Hollegaard, Mads Vilhelm

AU - Sørensen, Henrik Toft

AU - Hougaard, David Michael

AU - Konradsen, Helle Bossen

AU - Nørgaard, Mette

AU - Benfield, Thomas

PY - 2014/8/15

Y1 - 2014/8/15

N2 - Background. Most children are transiently colonized with Streptococcus pneumoniae, but very few develop invasive pneumococcal disease (IPD). Host genetic variation of innate immunity may predispose to IPD. We investigated the effect of genetic variation in the mannose-binding lectin gene, MBL2, on susceptibility and disease severity of IPD in previously healthy children aged <5 years. Methods. IPD cases were identified through national registries. DNA was obtained from the Danish Neonatal Screening Biobank. Pneumococcal serotypes were determined by Quellung reaction. The associations between MBL2 diplotypes and IPD susceptibility, serotypes, and outcome were investigated using logistic regression analysis. Results. We included 372 cases with meningitis, 907 with bacteremia, and 1263 age- and sex-matched controls; 2372 individuals were successfully genotyped and assigned MBL2 diplotypes. The median age in our combined case series was 13 months. Children with defective diplotypes were not at higher risk for meningitis than children with other diplotypes (odds ratio [OR], 0.85; 95% confidence interval [CI], .56-1.28). Similar results were found for bacteremia (OR, 0.89; 95% CI, .68-1.15) as well as for all cases (OR, 0.87; 95% CI, .70-1.09). There was no association with susceptibility to recurrent IPD (n = 12) for children with defective diplotypes compared with cases with a single episode (OR, 0.53; 95% CI, .07-4.13) and with all controls (OR, 0.46; 95% CI, .06-3.56). There was no association between diplotypes and mortality or between diplotypes and pneumococcal serotypes. Conclusions. Defective MBL2 polymorphisms did not predict increased IPD susceptibility in children born in Northern Europe.

AB - Background. Most children are transiently colonized with Streptococcus pneumoniae, but very few develop invasive pneumococcal disease (IPD). Host genetic variation of innate immunity may predispose to IPD. We investigated the effect of genetic variation in the mannose-binding lectin gene, MBL2, on susceptibility and disease severity of IPD in previously healthy children aged <5 years. Methods. IPD cases were identified through national registries. DNA was obtained from the Danish Neonatal Screening Biobank. Pneumococcal serotypes were determined by Quellung reaction. The associations between MBL2 diplotypes and IPD susceptibility, serotypes, and outcome were investigated using logistic regression analysis. Results. We included 372 cases with meningitis, 907 with bacteremia, and 1263 age- and sex-matched controls; 2372 individuals were successfully genotyped and assigned MBL2 diplotypes. The median age in our combined case series was 13 months. Children with defective diplotypes were not at higher risk for meningitis than children with other diplotypes (odds ratio [OR], 0.85; 95% confidence interval [CI], .56-1.28). Similar results were found for bacteremia (OR, 0.89; 95% CI, .68-1.15) as well as for all cases (OR, 0.87; 95% CI, .70-1.09). There was no association with susceptibility to recurrent IPD (n = 12) for children with defective diplotypes compared with cases with a single episode (OR, 0.53; 95% CI, .07-4.13) and with all controls (OR, 0.46; 95% CI, .06-3.56). There was no association between diplotypes and mortality or between diplotypes and pneumococcal serotypes. Conclusions. Defective MBL2 polymorphisms did not predict increased IPD susceptibility in children born in Northern Europe.

KW - Child, Preschool

KW - Denmark

KW - Disease Susceptibility

KW - Female

KW - Genetic Predisposition to Disease

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Male

KW - Mannose-Binding Lectin

KW - Pneumococcal Infections

KW - Polymorphism, Genetic

KW - Serogroup

KW - Streptococcus pneumoniae

U2 - 10.1093/cid/ciu276

DO - 10.1093/cid/ciu276

M3 - Journal article

C2 - 24771334

SN - 1058-4838

VL - 59

SP - e66-e71

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 4

ER -

Mannose-binding lectin gene, MBL2, polymorphisms are not associated with susceptibility to invasive pneumococcal disease in children

Abstract

Keywords

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