Investigation of malaria susceptibility determinants in the IFNG/IL26/IL22 genomic region.

Interferon-gamma, encoded by IFNG, is a key immunological mediator that is believed to play both a protective and a pathological role in malaria. Here, we investigate the relationship between IFNG variation and susceptibility to malaria. We began by analysing West African and European haplotype structure and patterns of linkage disequilibrium across a 100 kb genomic region encompassing IFNG and its immediate neighbours IL22 and IL26. A large case-control study of severe malaria in a West Africa population identified several weak associations with individual single-nucleotide polymorphisms in the IFNG and IL22 genes, and defined two IL22 haplotypes that are, respectively, associated with resistance and susceptibility. These data provide a starting point for functional and genetic analysis of the IFNG genomic region in malaria and other infectious and inflammatory conditions affecting African populations.