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Background  Severe malaria (SM) syndromes caused by  Plasmodium falciparum  infection result in major morbidity and mortality each year. However, only a fraction of  P. falciparum  infections develop into SM, implicating host genetic factors as important determinants of disease outcome. Previous studies indicate that tumour necrosis factor (TNF) and lymphotoxin alpha (LTα) may be important for the development of cerebral malaria (CM) and other SM syndromes.    Methods  An extensive analysis was conducted of single nucleotide polymorphisms (SNPs) in the  TNF, LTA  and  LTB  genes in highland Papuan children and adults, a population historically unexposed to malaria that has migrated to a malaria endemic region. Generated  P -values for SNPs spanning the  LTA/TNF/LTB  locus were corrected for multiple testing of all the SNPs and haplotype blocks within the region tested through 10,000 permutations. A global P-value of < 0.05 was considered statistically significant.    Results  No associations between SNPs in the  TNF/LTA/LTB  locus and susceptibility to SM in highland Papuan children and adults were found.    Conclusions  These results support the notion that unique selective pressure on the  TNF/LTA/LTB  locus in different populations has influenced the contribution of the gene products from this region to SM susceptibility.

A study of the TNF/LTA/LTB locus and susceptibility to severe malaria in highland papuan children and adults