Candidate polymorphisms and severe malaria in a Malian population.

Toure, O; Konate, S; Sissoko, S; Niangaly, A; Barry, A; Sall, AH; Diarra, E; Poudiougou, B; Sepulveda, N; Campino, SORCID logo; +5 more...Rockett, KA; Clark, TGORCID logo; Thera, MA; Doumbo, O; Collaboration with The MalariaGEN Consortium and (2012) Candidate polymorphisms and severe malaria in a Malian population. PloS one, 7 (9). e43987-. ISSN 1932-6203 DOI: 10.1371/journal.pone.0043987
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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.


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