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

Abstract

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.

Regulatory issues in immunity to liver and blood-stage malaria

“…Likewise, the Th2 subset aids in generating optimal antibody responses against plasmodium infections in humans and mice [32,37,38]. Th17 [39,40], Th22 [41], Tr27 [42], Tregs [43,44 ] and Tfh [45] have all been implicated in control of blood stage malaria. However, the contribution of none of these subsets has been as controversial as that of Tregs in malaria.…”

Functional Promoter Haplotypes of Interleukin-18 Condition Susceptibility to Severe Malarial Anemia and Childhood Mortality

“…The most common of these disease sequelae, severe malarial anemia (SMA), is responsible for the majority of the malariaassociated mortality in western Kenya (7,32,54). Based on historical presence of the disease, malaria has exerted a large impact on the human genome such that potentially harmful variants are preserved, largely because of the advantage offered in heterozygous individuals that are often protected from severe, complicated, and fatal malaria (14,19,21). Studies in our laboratory focused on variations in key cytokine genes have demonstrated associations between polymorphisms and SMA (4,37,38).…”

Interferon-γ (IFNG) microsatellite repeat and single nucleotide polymorphism haplotypes of IFN-α receptor (IFNAR1) associated with enhanced malaria susceptibility in Indian populations

“…Several polymorphisms (SNPs and microsatellite repeat) from the promoter, introns and UTR region of the IFNG gene have been reported (Koch et al, 2005). Some of these polymorphisms have been associated with diseases other than malaria in different world populations (Ding et al, 2008;Kim et al, 2012).…”