Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Genetic variation in cytokine promoter regions is postulated to influence susceptibility to infection, but the molecular mechanisms by which such polymorphisms might affect gene regulation are unknown. Through systematic DNA footprinting of the TNF (encoding tumour necrosis factor, TNF) promoter region, we have identified a single nucleotide polymorphism (SNP) that causes the helix-turn-helix transcription factor OCT-1 to bind to a novel region of complex protein-DNA interactions and alters gene expression in human monocytes. The OCT-1-binding genotype, found in approximately 5% of Africans, is associated with fourfold increased susceptibility to cerebral malaria in large case-control studies of West African and East African populations, after correction for other known TNF polymorphisms and linked HLA alleles.

Original publication




Journal article


Nat Genet

Publication Date





145 - 150


Animals, Binding Sites, Child, DNA-Binding Proteins, Gambia, Gene Expression Regulation, Genetic Predisposition to Disease, Genotype, Host Cell Factor C1, Humans, Kenya, Malaria, Cerebral, Malaria, Falciparum, Monocytes, Octamer Transcription Factor-1, Plasmodium falciparum, Polymorphism, Genetic, Promoter Regions, Genetic, Receptors, Tumor Necrosis Factor, Reference Values, Regression Analysis, Transcription Factors