Promoter Polymorphism of the Anion-Exchange Protein 1 Associated with Severe Malarial Anemia and Fatality

The anion-exchange protein 1 (AE1 or band 3) is involved in the erythrocyte invasion of the malaria parasite Plasmodium falciparum the adhesion of infected erythrocytes to endothelial cells, and the regulation of acid-base homeostasis, which is a critical factor for human survival in severe malaria. A variant of the AE1 gene promoter 512 base pairs (bp) distant from the transcription start site and 5699 bp from the translation start codon (AE1−5699T→C) has been shown to be highly frequent in a population from the Ashanti region, Ghana. In a matched-pair case-control study (736 pairs), children heterozygous for the mutation (AE1−5699CT) had an increased risk of severe malarial anemia (odds ratio [OR], 1.45 [95% confidence interval {CI}, 1.05–2.01]; P