Tumor necrosis factor and lymphotoxin-alpha polymorphisms and severe malaria in African populations.
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.
Clark
Taane G
TG
Wellcome Trust Centre for Human Genetics, University of Oxford, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, United Kingdom. tgc@well.ox.ac.uk
Diakite
Mahamadou
M
Auburn
Sarah
S
Campino
Susana
S
Fry
Andrew E
AE
Green
Angela
A
Richardson
Anna
A
Small
Kerrin
K
Teo
Yik Y
YY
Wilson
Jonathan
J
Jallow
Muminatou
M
Sisay-Joof
Fatou
F
Pinder
Margaret
M
Griffiths
Michael J
MJ
Peshu
Norbert
N
Williams
Thomas N
TN
Marsh
Kevin
K
Molyneux
Malcolm E
ME
Taylor
Terrie E
TE
Rockett
Kirk A
KA
Kwiatkowski
Dominic P
DP
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*
D008233:Lymphotoxin-alpha; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha