Candidate polymorphisms and severe malaria in a Malian population.

01 Jan 2012
Toure O, Konate S, Sissoko S, Niangaly A, Barry A, Sall AH, Diarra E, Poudiougou B, Sepulveda N, Campino S, Rockett KA, Clark TG, Thera MA, Doumbo O, Collaboration with The MalariaGEN Consortium.

Malaria is a major health burden in sub-Saharan African countries, including Mali. The disease is complex, with multiple genetic determinants influencing the observed variation in response to infection, progression, and severity. We assess the influence of sixty-four candidate loci, including the sickle cell polymorphism (HbS), on severe malaria in a case-control study consisting of over 900 individuals from Bamako, Mali. We confirm the known protective effects of the blood group O and the HbS AS genotype on life-threatening malaria. In addition, our analysis revealed a marginal susceptibility effect for the CD40 ligand (CD40L)+220C allele. The lack of statistical evidence for other candidates may demonstrate the need for large-scale genome-wide association studies in malaria to discover new polymorphisms. It also demonstrates the need for establishing the region-specific repertoire of functional variation in important genes, including the glucose-6-phosphatase deficiency gene, before embarking on focused genotyping.