title: Tumor necrosis factor and lymphotoxin-alpha polymorphisms and severe malaria in African populations.
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.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, United Kingdom. tgc@well.ox.ac.uk
authors.forename: Taane G
authors.initials: TG
authors.lastname: Clark
authors.forename: Mahamadou
authors.initials: M
authors.lastname: Diakite
authors.forename: Sarah
authors.initials: S
authors.lastname: Auburn
authors.forename: Susana
authors.initials: S
authors.lastname: Campino
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Fry
authors.forename: Angela
authors.initials: A
authors.lastname: Green
authors.forename: Anna
authors.initials: A
authors.lastname: Richardson
authors.forename: Kerrin
authors.initials: K
authors.lastname: Small
authors.forename: Yik Y
authors.initials: YY
authors.lastname: Teo
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wilson
authors.forename: Muminatou
authors.initials: M
authors.lastname: Jallow
authors.forename: Fatou
authors.initials: F
authors.lastname: Sisay-Joof
authors.forename: Margaret
authors.initials: M
authors.lastname: Pinder
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Griffiths
authors.forename: Norbert
authors.initials: N
authors.lastname: Peshu
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Williams
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.forename: Malcolm E
authors.initials: ME
authors.lastname: Molyneux
authors.forename: Terrie E
authors.initials: TE
authors.lastname: Taylor
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Rockett
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Kwiatkowski
mesh_terms: D000818:Animals; D002648:Child; D005714:Gambia; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007630:Kenya; D015810:Linkage Disequilibrium; D008233:Lymphotoxin-alpha / Q000235:genetics*; D016778:Malaria, Falciparum / Q000235:genetics*; D008295:Malawi; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D008233:Lymphotoxin-alpha; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha