title: Candidate polymorphisms and severe malaria in a Malian population.
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.
authors.affiliation: Malaria Research and Training Centre, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali.
authors.forename: Ousmane
authors.initials: O
authors.lastname: Toure
authors.forename: Salimata
authors.initials: S
authors.lastname: Konate
authors.forename: Sibiri
authors.initials: S
authors.lastname: Sissoko
authors.forename: Amadou
authors.initials: A
authors.lastname: Niangaly
authors.forename: Abdoulaye
authors.initials: A
authors.lastname: Barry
authors.forename: Abdourahmane H
authors.initials: AH
authors.lastname: Sall
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Diarra
authors.forename: Belco
authors.initials: B
authors.lastname: Poudiougou
authors.forename: Nuno
authors.initials: N
authors.lastname: Sepulveda
authors.forename: Susana
authors.initials: S
authors.lastname: Campino
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Rockett
authors.forename: Taane G
authors.initials: TG
authors.lastname: Clark
authors.forename: Mahamadou A
authors.initials: MA
authors.lastname: Thera
authors.forename: Ogobara
authors.initials: O
authors.lastname: Doumbo
mesh_terms: D000017:ABO Blood-Group System; D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D006451:Hemoglobin, Sickle / Q000235:genetics*; D006801:Humans; D007223:Infant; D008024:Ligands; D008288:Malaria / Q000235:genetics*; D008297:Male; D008302:Mali; D015233:Models, Statistical; D011110:Polymorphism, Genetic
chemical_list: D000017:ABO Blood-Group System; D006451:Hemoglobin, Sickle; D008024:Ligands; D005952:Glucose-6-Phosphatase