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.

Original publication

DOI

10.1086/596320

Type

Journal article

Journal

The Journal of infectious diseases

Publication Date

02/2009

Volume

199

Pages

569 - 575

Addresses

Wellcome Trust Centre for Human Genetics, University of Oxford, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, United Kingdom. tgc@well.ox.ac.uk

Keywords

Animals, Humans, Malaria, Falciparum, Genetic Predisposition to Disease, Tumor Necrosis Factor-alpha, Oligonucleotide Array Sequence Analysis, Haplotypes, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Child, Kenya, Malawi, Gambia, Lymphotoxin-alpha