Candidate polymorphisms and severe malaria in a Malian population.

• Main 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, Collaboration with The MalariaGEN Consortium
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2012-01-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC3434208?pdf=render

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.