An evaluation of concurrent G6PD (A-) deficiency and sickle cell trait in Malian populations of children with severe or uncomplicated P. falciparum malaria.

Sickle cell trait (SCT) and glucose-6-phosphate dehydrogenase (G6PD (A−)) deficiency are two common genetic conditions in sub-Saharan Africa. In Mali, SCT and G6PD (A−) deficiency are found at overall frequencies of 12% and 14%, respectively. While SCT and G6PD (A−) deficiency were associated with protection against severe malaria, we have examined the occurrence of the G6PD (A−) polymorphism and SCT together in Malian populations of children with severe or uncomplicated malaria. No evidence for increased protection was detected in children who carried both SCT and the G6PD (A−) polymorphism. A suggestion of greater susceptibility was instead observed for the heterozygous G6PD (A−) versus G6PD normal condition in SCT females (OR 15, = 0.003). While in addition, larger studies will be needed to further evaluate the possibility of interference between the protective effects of the SCT and G6PD (A−) conditions, we note that these results are reminiscent of the negative epistasis reported for the malaria-protective effects of α+-thalassemia and SCT. Better understanding of the conflicts among malaria-protective polymorphisms may shed light on their observed epidemiological distributions and improve our knowledge of the mechanisms by which they operate.