Tumour
necrosis factor (TNF) - α has been shown to play an important role in the pathogenesis of
falciparum malaria. Two TNF promoter polymorphisms, TNF-308 and TNF-238 have been associated with differential activity and production of TNF. In order to investigate the association between TNF-308 and TNF-238 and the clinical outcome of
malaria in a Nigerian population, the two TNF polymorphisms were analysed using Sequenom
iPLEX Platform. A total of 782 children; 283 children with uncomplicated
malaria, 255 children with severe
malaria and 244 children with
asymptomatic infection (controls) were studied. The distribution of TNF-308 and TNF-238 genotypes were consistent with the Hardy-Weinberg equilibrium. Distribution of both TNF polymorphisms differed significantly across all clinical groups (TNF-308: p=0.007; TNF-238: p=0.001). Further tests for association with severe
malaria using genotype models controlling for age, parasitaemia and HbAS showed a significant association of the TNF-238 polymorphism with susceptibility to severe
malaria (95% CI=1.43-6.02, OR=2.94, p=0.003237) The GG genotype of TNF-238 significantly increased the risk of developing
cerebral malaria from asymptomatic
malaria and uncomplicated
malaria (95% CI=1.99-18.17, OR=6.02, p<0.001 and 95% CI=1.78-8.23, OR=3.84, p<0.001 respectively). No significant association was found between TNF-308 and
malaria outcome. These results show thegenetic association of TNF-238 in the clinical outcome of
malaria in Ibadan, southwest Nigeria. These findings add support to the role of TNF in the outcome of
malaria infection. Further large scale studies across multiple
malaria endemic populations will be required to determine the specific roles of TNF-308 and TNF-238 in the outcome of
falciparum malaria infection.