Haemoglobin C protects against clinical Plasmodium falciparum malaria.

Haemoglobin C (HbC; β6Glu → Lys) is common in malarious areas of West Africa, especially in Burkina Faso1,2. Conclusive evidence exists on the protective role against severe malaria of haemoglobin S (HbS; β6Glu → Val) heterozygosity3, whereas conflicting results for the HbC trait have been reported4,5,6,7,8,9,10 and no epidemiological data exist on the possible role of the HbCC genotype. In vitro studies suggested that HbCC erythrocytes fail to support the growth of P. falciparum11,12 but HbC homozygotes with high P. falciparum parasitaemias have been observed10. Here we show, in a large case–control study performed in Burkina Faso on 4,348 Mossi subjects, that HbC is associated with a 29% reduction in risk of clinical malaria in HbAC heterozygotes (P = 0.0008) and of 93% in HbCC homozygotes (P = 0.0011). These findings, together with the limited pathology of HbAC and HbCC13 compared to the severely disadvantaged HbSS and HbSC genotypes and the low βS gene frequency in the geographic epicentre of βC1,2,14, support the hypothesis that, in the long term and in the absence of malaria control, HbC would replace HbS in central West Africa.