Candidate polymorphisms and severe malaria in a malian population |
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Authors: | Ousmane Toure Salimata Konate Sibiri Sissoko Amadou Niangaly Abdoulaye Barry Abdourahmane H Sall Elisabeth Diarra Belco Poudiougou Nuno Sepulveda Susana Campino Kirk A Rockett Taane G Clark Mahamadou A Thera Ogobara Doumbo;in collaboration with The MalariaGEN Consortium |
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Institution: | Malaria Research and Training Centre, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali. |
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Abstract: | 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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