Profound bias in interferon-gamma and interleukin-6 allele frequencies in western Kenya, where severe malarial anemia is common in children.

The intensity of malaria transmission is related to the pattern of malarial disease observed in different regions, but populations may also differ in their underlying predispositions to severe malarial anemia or cerebral malaria. In western Kenya, where severe malarial anemia is much more common than cerebral malaria, the distributions of tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, transforming growth factor (TGF)-beta, IL-6, and interferon (IFN)-gamma alleles were examined in a cohort of young men. The cohort displayed a marked bias toward genotypes associated with low expression of IFN-gamma and IL-6, cytokines that, at high levels, have been implicated in malarial anemia and poor malaria outcomes. By contrast, the frequency of the TNF-alpha -238A allele, which has been associated with severe malarial anemia, was found to be similar to the frequency previously reported in comparison populations in Africa and elsewhere. IFN-gamma and IL-6 genotypes may play roles in the development of severe malaria and could contribute to the relative frequency of severe malarial anemia or cerebral malaria in exposed populations.