A genetic association study in the Gambia using tagging polymorphisms in the major histocompatibility complex class III region implicates a HLA-B associated transcript 2 polymorphism in severe malaria susceptibility
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The tumour necrosis factor (TNF) gene and other genes flanking it in the major histocompatibility complex (MHC) class III region are potentially important mediators of both immunity and pathogenesis of malaria. We investigated the association of severe malaria with 11 haplotype tagging-polymorphisms for 11 MHC class III candidate genes, including TNF, lymphotoxin alpha (LTA), allograft inflammatory factor 1 (AIF1), and HLA-B associated transcript 2 (BAT2). An analysis of 2,162 case-controls demonstrated the first evidence of association between a BAT2 polymorphism (rs1046089) and severe malaria.
KeywordsMalaria Major Histocompatibility Complex Major Histocompatibility Complex Class Severe Malaria Cerebral Malaria
We thank the patients from the Gambian study population, as well as the many investigators involved in the original study for their contributions. We thank Bronwyn MacInnis and Daniel Alcock for providing useful comments on an earlier version of this manuscript. This work was funded by the UK Medical Research Council, Wellcome Trust, Bill and Melinda Gates Foundation and Grand Challenges in Global Health and a PhD training fellowship from the International Atomic Energy Agency (MD).
Conflict of interest statement
The authors declare that no conflict of interests exist.
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