Journal article
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, DI Stanisic, M Laman, A Carmagnac, S Allen, A O'Donnell, H Karunajeewa, A Rosanas-Urgell, P Siba, TME Davis, P Michon, L Schofield, K Rockett, D Kwiatkowski, I Mueller
Genes and Immunity | SPRINGERNATURE | Published : 2016
DOI: 10.1038/gene.2015.50
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 cytok..
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Grants
Awarded by Royal Australasian College of Physicians
Funding Acknowledgements
We gratefully acknowledge the assistance of staff on the Paediatric Ward at Modilon Hospital, the Papua New Guinea Institute of Medical Research staff at Modilon Hospital and the Yagaum campus, and the patients and their families for their participation. MalariaGEN is supported by the Wellcome Trust (WT077383/Z/05/Z) and by the Foundation for the National Institutes of Health (566) as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative. The Resource Centre for Genomic Epidemiology of Malaria is supported by the Wellcome Trust (090770/Z/09/Z). Support was also provided by the Medical Research Council (G0600718). The Wellcome Trust also provides core awards to the Wellcome Trust Centre for Human Genetics (090532/Z/09/Z) and to the Wellcome Trust Sanger Institute (098051). Financial support for this study was also obtained from the National Health and Medical Research Council (NHMRC) of Australia (project grants 513782 and 516735 and program grant 637406). LS was supported by an International Research Scholarship of the Howard Hughes Medical Institute. LM was supported by Royal Australasian College of Physicians (Basser) and NHMRC scholarships, ML a Fogarty Foundation scholarship and TMED an NHMRC Practitioner Fellowship.