{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T20:02:14Z","timestamp":1762459334581,"version":"3.41.2"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2016,11,11]],"date-time":"2016-11-11T00:00:00Z","timestamp":1478822400000},"content-version":"vor","delay-in-days":680,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Background. \u2003Neisseria meningitidis is the cause of meningococcal bacteremia and meningitis, and nasopharyngeal colonization with this pathogen is common. The incidence of invasive disease is highest in infants, whereas adolescents more often are carriers. Altered regulation or dysfunction of the innate immune system may predispose to invasive meningococcal disease (IMD). In this study, we investigated the effect of genetic variation in the mannose-binding lectin gene, MBL2, and its promoter on susceptibility to IMD and IMD-associated mortality among children.<\/jats:p>\n               <jats:p>Methods. \u2003Children (&amp;lt;5 years) diagnosed during 1982\u20132007 with IMD and controls were identified through Danish national registries. DNA was obtained from the Danish Neonatal Screening Biobank. The associations between MBL2 diplotypes and IMD susceptibility and 30- and 90-day mortality were investigated using logistic regression analysis.<\/jats:p>\n               <jats:p>Results. \u2003We included 1351 children: 406 with meningitis, 272 with bacteremia, and 673 age- and sex-matched controls. Of the children studied, 1292 (96%) were successfully genotyped and assigned MBL2 diplotypes. The median age in IMD cases was 19.1 months (interquartile range [IQR], 8.8\u201332.2 months). Children with defective MBL2 diplotypes were not at higher risk for meningococcal meningitis than children with intermediate and normal diplotypes (odds ratio [OR] = 0.69; 95% confidence interval [CI], .47\u20131.02). Similar results were found for children with bacteremia and defective diplotypes (OR = 0.84; 95% CI, .53\u20131.32) as well as for all cases (OR = 0.75; 95% CI, .56\u20131.01). There was no association between MBL2 diplotypes and mortality.<\/jats:p>\n               <jats:p>Conclusions. \u2003Defective MBL2 diplotypes did not predict either an increased IMD susceptibility or mortality in a Danish population of children.<\/jats:p>","DOI":"10.1093\/ofid\/ofv127","type":"journal-article","created":{"date-parts":[[2015,9,2]],"date-time":"2015-09-02T00:29:18Z","timestamp":1441153758000},"source":"Crossref","is-referenced-by-count":15,"title":["Mannose-Binding Lectin Gene, MBL2, Polymorphisms Do Not Increase Susceptibility to Invasive Meningococcal Disease in a Population of Danish Children"],"prefix":"10.1093","volume":"2","author":[{"given":"Lene F.","family":"Lundbo","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases"},{"name":"Clinical Research Centre, Hvidovre Hospital"},{"name":"Faculty of Health Sciences, University of Copenhagen"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik T.","family":"S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Aarhus University Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise N.","family":"Clausen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mads V.","family":"Hollegaard","sequence":"additional","affiliation":[{"name":"Danish Centre for Neonatal Screening, Department for Congenital Disorders"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Hougaard","sequence":"additional","affiliation":[{"name":"Danish Centre for Neonatal Screening, Department for Congenital Disorders"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helle B.","family":"Konradsen","sequence":"additional","affiliation":[{"name":"Division of Diagnostics and Infection Control"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zitta Barrella","family":"Harboe","sequence":"additional","affiliation":[{"name":"Department of Microbiological Surveillance and Research, Statens Serum Institut, Copenhagen"},{"name":"Department for Pulmonary and Infectious Diseases, North Zealand Hospital Hiller\u00f8d, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mette","family":"N\u00f8rgaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Aarhus University Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Benfield","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases"},{"name":"Clinical Research Centre, Hvidovre Hospital"},{"name":"Faculty of Health Sciences, University of Copenhagen"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,9,1]]},"reference":[{"issue":"(suppl 2)","key":"2020081009270547100_OFV127C1","doi-asserted-by":"crossref","first-page":"B3","DOI":"10.1016\/j.vaccine.2011.12.062","article-title":"Meningococcal disease: clinical presentation and sequelae","volume":"30","author":"Pace","year":"2012","journal-title":"Vaccine"},{"key":"2020081009270547100_OFV127C2","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1017\/S0950268800066449","article-title":"The Stonehouse survey: nasopharyngeal carriage of meningococci and Neisseria lactamica","volume":"99","author":"Cartwright","year":"1987","journal-title":"Epidemiol Infect"},{"key":"2020081009270547100_OFV127C3","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1086\/428590","article-title":"Genetic analysis of meningococci carried by children and young adults","volume":"191","author":"Claus","year":"2005","journal-title":"J Infect Dis"},{"key":"2020081009270547100_OFV127C4","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S1473-3099(08)70261-5","article-title":"Host genetic susceptibility to pneumococcal and meningococcal disease: a systematic review and meta-analysis","volume":"9","author":"Brouwer","year":"2009","journal-title":"Lancet Infect Dis"},{"key":"2020081009270547100_OFV127C5","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1164\/rccm.200702-169OC","article-title":"IkappaB genetic polymorphisms and invasive pneumococcal disease","volume":"176","author":"Chapman","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"key":"2020081009270547100_OFV127C6","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1086\/606054","article-title":"Mannose-binding lectin is a critical factor in systemic complement activation during meningococcal septic shock","volume":"49","author":"Sprong","year":"2009","journal-title":"Clin Infect Dis"},{"key":"2020081009270547100_OFV127C7","doi-asserted-by":"crossref","first-page":"3784","DOI":"10.4049\/jimmunol.172.6.3784","article-title":"Mannose-binding lectin binds to two major outer membrane proteins, opacity protein and porin, of Neisseria meningitidis","volume":"172","author":"Estabrook","year":"2004","journal-title":"J Immunol"},{"key":"2020081009270547100_OFV127C8","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1086\/379324","article-title":"Impact of mannose-binding lectin on susceptibility to infectious diseases","volume":"37","author":"Eisen","year":"2003","journal-title":"Clin Infect Dis"},{"key":"2020081009270547100_OFV127C9","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/sj.gene.6364283","article-title":"Mannose-binding lectin and its genetic variants","volume":"7","author":"Garred","year":"2006","journal-title":"Genes Immun"},{"key":"2020081009270547100_OFV127C10","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1084\/jem.20040111","article-title":"A population-based study of morbidity and mortality in mannose-binding lectin deficiency","volume":"199","author":"Dahl","year":"2004","journal-title":"J Exp Med"},{"key":"2020081009270547100_OFV127C11","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1111\/1469-0691.12745","article-title":"MBL2 deficiency is associated with higher genomic bacterial loads during meningococcemia in young children","volume":"20","author":"Darton","year":"2014","journal-title":"Clin Microbiol Infect"},{"key":"2020081009270547100_OFV127C12","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1097\/01.inf.0000256751.76218.7c","article-title":"Age-dependent association of human mannose-binding lectin mutations with susceptibility to invasive meningococcal disease in childhood","volume":"26","author":"Faber","year":"2007","journal-title":"Pediatr Infect Dis J"},{"key":"2020081009270547100_OFV127C13","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1001\/jama.285.10.1316","article-title":"Acute respiratory tract infections and mannose-binding lectin insufficiency during early childhood","volume":"285","author":"Koch","year":"2001","journal-title":"JAMA"},{"key":"2020081009270547100_OFV127C14","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s10654-014-9930-3","article-title":"The Danish Civil Registration System as a tool in epidemiology","volume":"29","author":"Schmidt","year":"2014","journal-title":"Eur J Epidemiol"},{"key":"2020081009270547100_OFV127C15","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1007\/s10545-007-0631-x","article-title":"Storage policies and use of the Danish Newborn Screening Biobank","volume":"30","author":"N\u00f8rgaard-Pedersen","year":"2007","journal-title":"J Inherit Metab 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whole-genome-amplified DNA from 3- to 25-year-old neonatal dried blood spot samples with reference to fresh genomic DNA","volume":"30","author":"Hollegaard","year":"2009","journal-title":"Electrophoresis"},{"key":"2020081009270547100_OFV127C20","doi-asserted-by":"crossref","first-page":"e66","DOI":"10.1093\/cid\/ciu276","article-title":"Mannose-binding lectin gene, MBL2, polymorphisms are not associated with susceptibility to invasive pneumococcal disease in children","volume":"59","author":"Lundbo","year":"2014","journal-title":"Clin Infect Dis"},{"key":"2020081009270547100_OFV127C21","doi-asserted-by":"crossref","first-page":"e42113","DOI":"10.1371\/journal.pone.0042113","article-title":"Mannose-binding lectin deficiency is associated with myocardial infarction: the HUNT2 study in Norway","volume":"7","author":"Vengen","year":"2012","journal-title":"PLoS 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