Tumor necrosis factor and lymphotoxin-alpha polymorphisms and severe malaria in African populations.


Clark, TG; Diakite, M; Auburn, S; Campino, S; Fry, AE; Green, A; Richardson, A; Small, K; Teo, YY; Wilson, J; Jallow, M; Sisay-Joof, F; Pinder, M; Griffiths, MJ; Peshu, N; Williams, TN; Marsh, K; Molyneux, ME; Taylor, TE; Rockett, KA; Kwiatkowski, DP; (2009) Tumor necrosis factor and lymphotoxin-alpha polymorphisms and severe malaria in African populations. The Journal of infectious diseases, 199 (4). pp. 569-75. ISSN 0022-1899 DOI: https://doi.org/10.1086/596320

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Abstract

The tumor necrosis factor gene (TNF) and lymphotoxin-alpha gene (LTA) have long attracted attention as candidate genes for susceptibility traits for malaria, and several of their polymorphisms have been found to be associated with severe malaria (SM) phenotypes. In a large study involving >10,000 individuals and encompassing 3 African populations, we found evidence to support the reported associations between the TNF -238 polymorphism and SM in The Gambia. However, no TNF/LTA polymorphisms were found to be associated with SM in cohorts in Kenya and Malawi. It has been suggested that the causal polymorphisms regulating the TNF and LTA responses may be located some distance from the genes. Therefore, more-detailed mapping of variants across TNF/LTA genes and their flanking regions in the Gambian and allied populations may need to be undertaken to find any causal polymorphisms.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Faculty of Infectious and Tropical Diseases > Dept of Disease Control
Research Centre: Malaria Centre
PubMed ID: 19281305
Web of Science ID: 262802200015
URI: http://researchonline.lshtm.ac.uk/id/eprint/4457

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