Investigating the genetic basis of the lower susceptibility to malaria shown by the Fulani of West-Africa.

Despite equivalent exposure to infection and comparable use of protective measures, the Fulani of West Africa have been shown to mount stronger immune responses to Plasmodium falciparum antigens and to be less susceptible to infection and mild disease than sympatric populations. The Fulani also show a higher response to other pathogens, and both their Th1 and Th2 responses are enhanced, suggesting that their resistance to malaria could result from a generally stronger immune activation. Key genes related to T regulatory cell function are indeed down-regulated in the Fulani. This disorder of immune homeostasis could be driven by genetic factors positively selected by P. falciparum and may underlie the reported higher susceptibility of the Fulani to autoimmune diseases. In order to investigate the genetic basis of the lower susceptibility to malaria shown by the Fulani we conducted a large-scale epidemiological study in Burkina Faso consisting of a combination of cross-sectional and longitudinal surveys. We genotyped 363 Single Nucleotide Polymorphisms (SNPs) on 2186 samples, by Sequenom MassArray System. SNPs included polymorphisms previously shown to be involved in resistance to severe malaria, in resistance to infection or in antibody production (www.malariagen.net), as well as polymorphisms at autoimmunity loci. We will show results of: i) inter-ethnic comparison of malaria susceptibility phenotypes; ii) population genetics analysis; iii) genetic association analysis with parasitological, clinical and immunological phenotypes.