Cytokine gene haplotypes with a potential effect on susceptibility to malaria in sympatric ethnic groups in Mali

Abstract

Cytokines are important players in the immune responses, and an unbalance in pro- and anti-inflammatory cytokine responses may affect parasitemia and pathology in a Plasmodium falciparum infection. Polymorphisms in cytokine genes may affect not only the levels of the protein, but many down-stream functions, such as production of C-reactive protein and immunoglobulin isotype switching. Susceptibility to malaria has been shown to differ between individuals with different genetic backgrounds, as indicated by studies in Fulani and non-Fulani ethnic groups. The aim of this study was to investigate possible interethnic differences in totally twelve single nucleotide polymorphisms (SNPs) in the genes encoding the cytokines IL-1β, IL-6, IL-10 and TNF. These SNPs are present in the promoter region of the genes, and have previously been associated with cytokine expression and with disease outcome in malaria. The results from the present study suggest that the Fulani ethnic group has a more pro-inflammatory response, due to high frequencies of high-producing alleles of IL1β and low-producing alleles of IL10. IL-6 could potentially also contribute to the relatively lower susceptibility to malaria in the Fulani ethnic group, whereas the TNF polymorphisms analysed in this study rather seem to associate with the severity of the infection and not the susceptibility for the infection itself. We therefore suggest that the polymorphisms analysed in this study all show a potential to influence the relatively lower susceptibility to malaria seen in the Fulani ethnic group as compared to the other sympatric ethnic groups.