TNF alpha*2 marks high risk of severe disease during Plasmodium falciparummalaria and other infections in Sri Lankans

We have investigated the association between alleles of the genes for tumou r necrosis factor-alpha (TNF-alpha) and TNF-beta and severity of disease du ring malarial (Plasmodium falciparum) and other infections in the Sri Lanka n population. Patients were categorized as having either (i) uncomplicated malaria, (ii) severe and complicated malaria, or (iii) severe and complicat ed infection in which a diagnosis of malaria had been excluded. For all the patients, as well as for a group of matched healthy controls, TNF-alpha an d TNF-beta allelic types were identified using the polymerase chain reactio n (PCR) and allele-specific oligonucleotide probes and restriction enzyme d igestion. The odds in favour of carrying the TNF alpha*2 allele, mainly of the heterozygous genotype (TNF alpha*1, *2), were two to three times greate r among individuals with severe disease, of either malarial or other infect ious origin, relative to healthy controls or to those with uncomplicated ma larial infections. No significant risk was associated with either of the al leles of TNF-beta.