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dc.contributor.authorManning, L.
dc.contributor.authorCutts, J.
dc.contributor.authorStanisic, Danielle
dc.contributor.authorLaman, M.
dc.contributor.authorCarmagnac, A.
dc.contributor.authorAllen, S.
dc.contributor.authorO'Donnell, A.
dc.contributor.authorKarunajeewa, H.
dc.contributor.authorRosanas-Urgell, Anna
dc.contributor.authorM. Siba, Peter
dc.contributor.authorDavis, T.
dc.contributor.authorMichon, P.
dc.contributor.authorSchofield, L.
dc.contributor.authorRockett, K.
dc.contributor.authorKwiatkowski, D.
dc.contributor.authorMueller, I.
dc.date.accessioned2018-07-16T05:08:19Z
dc.date.available2018-07-16T05:08:19Z
dc.date.issued2016
dc.identifier.issn1476-5470
dc.identifier.doi10.1038/gene.2015.50
dc.identifier.urihttp://hdl.handle.net/10072/99987
dc.description.abstractGenetic factors are likely to contribute to low severe malaria case fatality rates in Melanesian populations, but association studies can be underpowered and may not provide plausible mechanistic explanations if significant associations are detected. In preparation for a genome-wide association study, 29 candidate single-nucleotide polymorphisms (SNPs) with minor allele frequencies >5% were examined in a case–control study of 504 Papua New Guinean children with severe malaria. In parallel, an immunological substudy was performed on convalescent peripheral blood mononuclear cells (PBMCs) from cases and controls. Following stimulation with a Toll-like receptor (TLR) 1/2 agonist, effector cytokines and chemokines were assayed. The only significant genetic association observed involved a nonsynonymous SNP (TLR1rs4833095) in the TLR1 gene. A recessive (TT) genotype was associated with reduced odds of severe malaria of 0.52 (95% confidence interval (0.29–0.90), P=0.006). Concentrations of pro-inflammatory cytokines interleukin-1β and tumour necrosis factor α were significantly higher in severe malaria cases compared with healthy controls, but lower in children with the protective recessive (TT) genotype. A genetic variant in TLR1 may contribute to the low severe malaria case fatality rates in this region through a reduced pro-inflammatory cellular phenotype.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNature Publishing
dc.relation.ispartofpagefrom52
dc.relation.ispartofpageto59
dc.relation.ispartofjournalGenes and Immunity
dc.relation.ispartofvolume17
dc.subject.fieldofresearchImmunology
dc.subject.fieldofresearchImmunology not elsewhere classified
dc.subject.fieldofresearchcode3204
dc.subject.fieldofresearchcode320499
dc.titleA Toll-like receptor-1 variant and its characteristic cellular phenotype is associated with severe malaria in Papua New Guinean children
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorStanisic, Danielle


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