Evidence map›Paper›PMID 37287037›Full record

Trial reportMalaria journal2023

Genetic variants of TLR4, including the novel variant, rs5030719, and related genes are associated with susceptibility to clinical malaria in African children.

Amir Ariff, Yong Song, Ruth Aguilar, Augusto Nhabomba, Maria Nelia Manaca, Siew-Kim Khoo, Selma Wiertsema, Quique Bassat, Arnoldo Barbosa, Llorenç Quintó and 6 more

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Malaria journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00231452 (Age of Exposure and Immunity to Malaria in Infants), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.6field-weighted citation impact, top 31% 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.

NCT00231452 nacompletednot on this map

Age of Exposure and Immunity to Malaria in Infants

TypeinterventionalSponsorHospital Clinic of BarcelonaRan2005 to 2009Enrolled349ConditionsMalariaArmsSulfadoxine-pyrimethamine (SP) + Artesunate (AS)
3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

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 7 institutions in 3 countries.

Amir AriffCentre for Genetic Origins of Health and Disease, The University of Western Australia and Curtin University, Perth, WA, 6009, Australia.
Yong SongCentre for Genetic Origins of Health and Disease, The University of Western Australia and Curtin University, Perth, WA, 6009, Australia.
Ruth AguilarISGlobal, Hospital Clínic of Barcelona, Universitat de Barcelona, 08036, Barcelona, Spain.
Augusto NhabombaCentro de Investigação em Saúde de Manhiça (CISM), 1929, Maputo, Mozambique.
Maria Nelia ManacaCentro de Investigação em Saúde de Manhiça (CISM), 1929, Maputo, Mozambique.
Siew-Kim KhooDivision of Cardiovascular and Respiratory Sciences, The University of Western Australia, Perth, WA, 6009, Australia.
Selma WiertsemaDivision of Cardiovascular and Respiratory Sciences, The University of Western Australia, Perth, WA, 6009, Australia.
Quique BassatISGlobal, Hospital Clínic of Barcelona, Universitat de Barcelona, 08036, Barcelona, Spain.
Arnoldo BarbosaCentro de Investigação em Saúde de Manhiça (CISM), 1929, Maputo, Mozambique.
Llorenç QuintóISGlobal, Hospital Clínic of Barcelona, Universitat de Barcelona, 08036, Barcelona, Spain.
Ingrid A LaingDivision of Cardiovascular and Respiratory Sciences, The University of Western Australia, Perth, WA, 6009, Australia.
Caterina GuinovartISGlobal, Hospital Clínic of Barcelona, Universitat de Barcelona, 08036, Barcelona, Spain.
Pedro L AlonsoISGlobal, Hospital Clínic of Barcelona, Universitat de Barcelona, 08036, Barcelona, Spain.
Carlota Dobaño *ISGlobal, Hospital Clínic of Barcelona, Universitat de Barcelona, 08036, Barcelona, Spain.
Peter Le Souëf *Division of Cardiovascular and Respiratory Sciences, The University of Western Australia, Perth, WA, 6009, Australia. peter.lesouef@uwa.edu.au.
Guicheng Zhang *Centre for Genetic Origins of Health and Disease, The University of Western Australia and Curtin University, Perth, WA, 6009, Australia. Brad.zhang@curtin.edu.au.
Manhiça Health Research Centre · MZBarcelona Institute for Global Health · ESCurtin University · AUThe Kids Research Institute Australia · AUThe University of Western Australia · AUUniversitat de Barcelona · ESUNSW Sydney · AU

Funding

Centro de Excelencia Severo Ochoa CEX2018-000806-SEU Framework Program 6 STREP 18902Instituto de Salud Carlos III A107190024Ministerio de Ciencia e Innovación SAF2005-25642-EMinisterio de Ciencia e Innovación SAF2008-00743
6 · The paper itself

Abstract

backgroundMalaria is a deadly disease caused by Plasmodium spp. Several blood phenotypes have been associated with malarial resistance, which suggests a genetic component to immune protection.

methodsOne hundred and eighty-seven single nucleotide polymorphisms (SNPs) in 37 candidate genes were genotyped and investigated for associations with clinical malaria in a longitudinal cohort of 349 infants from Manhiça, Mozambique, in a randomized controlled clinical trial (RCT) (AgeMal, NCT00231452). Malaria candidate genes were selected according to involvement in known malarial haemoglobinopathies, immune, and pathogenesis pathways.

resultsStatistically significant evidence was found for the association of TLR4 and related genes with the incidence of clinical malaria (p = 0.0005). These additional genes include ABO, CAT, CD14, CD36, CR1, G6PD, GCLM, HP, IFNG, IFNGR1, IL13, IL1A, IL1B, IL4R, IL4, IL6, IL13, MBL, MNSOD, and TLR2. Of specific interest, the previously identified TLR4 SNP rs4986790 and the novel finding of TRL4 SNP rs5030719 were associated with primary cases of clinical malaria.

conclusionsThese findings highlight a potential central role of TLR4 in clinical malarial pathogenesis. This supports the current literature and suggests that further research into the role of TLR4, as well as associated genes, in clinical malaria may provide insight into treatment and drug development.

Indexed as

MalariaToll-Like Receptor 4Genetic Predisposition to DiseaseGenotypeHumansInterleukin-13Polymorphism, Single NucleotideInterleukin-13TLR4 protein, humanToll-Like Receptor 4AfricaGenetic polymorphismsHaplotype trend regressionMalariars5030719TLR4

Identifiers

PMID37287037
PMCPMC10245343
OpenAlexW4379768032

What OpenQuestion holds

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Registered trials

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.