Evidence map›Paper›PMID 26633000›Full record

ArticleGenes and immunity

A Toll-like receptor-1 variant and its characteristic cellular phenotype is associated with severe malaria in Papua New Guinean children.

L Manning, J Cutts, D I Stanisic, M Laman, A Carmagnac, S Allen, A O'Donnell, H Karunajeewa, A Rosanas-Urgell, P Siba and 6 more

Open access · bronzeAbstract read
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In one paragraph

Article in Genes and immunity. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.0field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 14 citations in OpenAlex.

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  9. A preliminary assessment ofPapua and New Guinea medical journal
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 9 institutions in 5 countries.

L ManningSchool of Medicine and Pharmacology, University of Western Australia, Harry Perkins Institute, Fiona Stanley Hospital, Bull Creek, Western Australia, Australia.
J CuttsInfection and Immunity Division, Walter & Eliza Hall Institute, Parkville, Melbourne, Australia.
D I StanisicInfection and Immunity Division, Walter & Eliza Hall Institute, Parkville, Melbourne, Australia.
M LamanSchool of Medicine and Pharmacology, University of Western Australia, Harry Perkins Institute, Fiona Stanley Hospital, Bull Creek, Western Australia, Australia.
A CarmagnacInfection and Immunity Division, Walter & Eliza Hall Institute, Parkville, Melbourne, Australia.
S AllenLiverpool School of Tropical Medicine, Liverpool, UK.
A O'DonnellWeatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
H KarunajeewaInfection and Immunity Division, Walter & Eliza Hall Institute, Parkville, Melbourne, Australia.
A Rosanas-UrgellPapua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
P SibaPapua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
T M E DavisSchool of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia.
P MichonInfection and Immunity Division, Walter & Eliza Hall Institute, Parkville, Melbourne, Australia.
L SchofieldInfection and Immunity Division, Walter & Eliza Hall Institute, Parkville, Melbourne, Australia.
K RockettWellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK and Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
D KwiatkowskiWellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK and Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
I MuellerInfection and Immunity Division, Walter & Eliza Hall Institute, Parkville, Melbourne, Australia.
Walter and Eliza Hall Institute of Medical Research · AUPapua New Guinea Institute of Medical Research · PGCentre for Human Genetics · GBFiona Stanley Hospital · AUFremantle Hospital · AUGriffith University · AULiverpool School of Tropical Medicine · GBMRC Weatherall Institute of Molecular Medicine · GBWellcome Sanger Institute · GB

Funding

Howard Hughes Medical InstituteMedical Research Council G0600718Medical Research Council MR/M006212/1Wellcome Trust 090532/Z/09/ZWellcome Trust 090770Wellcome Trust 090770/Z/09/ZWellcome Trust 098051Wellcome Trust WT077383/Z/05/Z
6 · The paper itself

Abstract

Genetic 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.

Indexed as

Case-Control StudiesChild, PreschoolFemaleGenome-Wide Association StudyHumansLeukocytes, MononuclearMalaria, FalciparumMalePapua New GuineaPolymorphism, Single NucleotideToll-Like Receptor 1Toll-Like Receptor 1

Identifiers

PMID26633000
OpenAlexW2182798158

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.