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

Taane G. Clark, Mahamadou Diakite, Sarah Auburn, Susana Campino, Andrew E. Fry, Angela Green, Anna Richardson, Kerrin Small, Yik Y. Teo, Jonathan Wilson, Muminatou Jallow, Fatou Sisay-Joof, Margaret Pinder, Michael J. Griffiths, Norbert Peshu, Thomas N. Williams, Kevin Marsh, Malcolm E. Molyneux, Terrie E. Taylor, Kirk A. RockettDominic P. Kwiatkowski

Research output: Contribution to journalArticle

Abstract

The tumor necrosis factor gene (TNF) and lymphotoxin-α 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.

Original languageEnglish
Pages (from-to)569-575
Number of pages7
JournalJournal of Infectious Diseases
Volume199
Issue number4
DOIs
Publication statusPublished - 2009
Externally publishedYes

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    Clark, T. G., Diakite, M., Auburn, S., Campino, S., Fry, A. E., Green, A., Richardson, A., Small, K., Teo, Y. Y., Wilson, J., Jallow, M., Sisay-Joof, F., Pinder, M., Griffiths, M. J., Peshu, N., Williams, T. N., Marsh, K., Molyneux, M. E., Taylor, T. E., ... Kwiatkowski, D. P. (2009). Tumor necrosis factor and lymphotoxin-α polymorphisms and severe malaria in African populations. Journal of Infectious Diseases, 199(4), 569-575. https://doi.org/10.1086/596320