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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis
Nature Genetics, Volume 39, No. 4, Year 2007
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Description
Toll-like receptors (TLRs) and members of their signaling pathway are important in the initiation of the innate immune response to a wide variety of pathogens. The adaptor protein Mal (also known as TIRAP), encoded by TIRAP (MIM 606252), mediates downstream signaling of TLR2 and TLR4 (refs. 4-6). We report a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis. We genotyped 33 SNPs, including rs8177374, which encodes a leucine substitution at Ser180 of Mal. We found that heterozygous carriage of this variant associated independently with all four infectious diseases in the different study populations. Combining the study groups, we found substantial support for a protective effect of S180L heterozygosity against these infectious diseases (N = 6,106; overall P = 9.6 × 10-8). We found that the Mal S180L variant attenuated TLR2 signal transduction. © 2007 Nature Publishing Group.
Authors & Co-Authors
Khor, Chiea Chuen
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
United Kingdom, London
Hammersmith Hospital
Singapore, Singapore City
A-star, Singapore Institute for Clinical Sciences
Chapman, Stephen J.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
United Kingdom, Oxford
Churchill Hospital
Vannberg, Fredrik O.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Dunne, Aisling
Ireland, Dublin
Trinity College Dublin
Murphy, Caroline
Ireland, Dublin
Trinity College Dublin
Ling, Edmund Y.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Frodsham, A.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Walley, Andrew J.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
United Kingdom, London
Hammersmith Hospital
Kyrieleis, Otto
Ireland, Dublin
Trinity College Dublin
Khan, Amir
Ireland, Dublin
Trinity College Dublin
Aucan, Christophe
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Segal, Shelley
United Kingdom, Oxford
John Radcliffe Hospital
Moore, Catrin E.
United Kingdom, Oxford
John Radcliffe Hospital
Knox, Kyle
United Kingdom, Oxford
John Radcliffe Hospital
Campbell, Sarah J.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Lienhardt, Christian
Senegal, Dakar
Institut de Recherche Pour le Développement Dakar
Scott, A.
Kenya, Kilifi
Centre for Geographic Medicine Research
Aaby, Peter
Guinea-bissau, Bissau
Bandim Health Project
Sow, Oumou Younoussa
Guinea
University Ignace Deen
Grignani, Robert T.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
United Kingdom, London
Hammersmith Hospital
Singapore, Singapore City
A-star, Singapore Institute for Clinical Sciences
Sillah, Jackson S.
Gambia, Banjul
Medical Research Council Laboratories Gambia
Sirugo, G.
Gambia, Banjul
Medical Research Council Laboratories Gambia
Peshu, Norbert M.
Kenya, Kilifi
Centre for Geographic Medicine Research
Williams, Thomas Neil
Kenya, Kilifi
Centre for Geographic Medicine Research
Maitland, Kathryn M.
Kenya, Kilifi
Centre for Geographic Medicine Research
Davies, Robert J.O.
United Kingdom, Oxford
Churchill Hospital
Kwiatkowski, Dominic P.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
United Kingdom, Oxford
John Radcliffe Hospital
Gambia, Banjul
Medical Research Council Laboratories Gambia
Day, Nichloas P.J.
Viet Nam, Ho Chi Minh City
Cho Quan Hospital
Yala, Djamel
Algeria, Algiers
Institut Pasteur - Alger
Crook, Derrick W.
United Kingdom, Oxford
John Radcliffe Hospital
Marsh, Kevin
Kenya, Kilifi
Centre for Geographic Medicine Research
Berkley, James A.
United Kingdom, Oxford
Churchill Hospital
O'Neill, Luke A.J.
Ireland, Dublin
Trinity College Dublin
Hill, Adrian V. S.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Statistics
Citations: 34
Authors: 34
Affiliations: 13
Identifiers
Doi:
10.1038/ng1976
ISSN:
10614036
e-ISSN:
15461718
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Case-Control Study