title: Haemoglobin C protects against clinical Plasmodium falciparum malaria.
abstract: Haemoglobin C (HbC; beta6Glu --> Lys) is common in malarious areas of West Africa, especially in Burkina Faso. Conclusive evidence exists on the protective role against severe malaria of haemoglobin S (HbS; beta6Glu --> Val) heterozygosity, whereas conflicting results for the HbC trait have been reported 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. falciparum but HbC homozygotes with high P. falciparum parasitaemias have been observed. 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 HbCC compared to the severely disadvantaged HbSS and HbSC genotypes and the low betaS gene frequency in the geographic epicentre of betaC, support the hypothesis that, in the long term and in the absence of malaria control, HbC would replace HbS in central West Africa.
authors.affiliation: Dipartimento di Scienze di Sanità Pubblica, Sezione di Parassitologia, WHO Collaborating Centre for Malaria Epidemiology and Control, University of Rome "La Sapienza", 00185, Rome, Italy. david.modiano@uniroma1.it
authors.forename: D
authors.initials: D
authors.lastname: Modiano
authors.forename: G
authors.initials: G
authors.lastname: Luoni
authors.forename: B S
authors.initials: BS
authors.lastname: Sirima
authors.forename: J
authors.initials: J
authors.lastname: Simporé
authors.forename: F
authors.initials: F
authors.lastname: Verra
authors.forename: A
authors.initials: A
authors.lastname: Konaté
authors.forename: E
authors.initials: E
authors.lastname: Rastrelli
authors.forename: A
authors.initials: A
authors.lastname: Olivieri
authors.forename: C
authors.initials: C
authors.lastname: Calissano
authors.forename: G M
authors.initials: GM
authors.lastname: Paganotti
authors.forename: L
authors.initials: L
authors.lastname: D'Urbano
authors.forename: I
authors.initials: I
authors.lastname: Sanou
authors.forename: A
authors.initials: A
authors.lastname: Sawadogo
authors.forename: G
authors.initials: G
authors.lastname: Modiano
authors.forename: M
authors.initials: M
authors.lastname: Coluzzi
mesh_terms: D000293:Adolescent; D000354:Africa, Western; D000818:Animals; D002050:Burkina Faso; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005787:Gene Frequency; D006444:Hemoglobin C / Q000235:genetics / Q000502:physiology*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D016778:Malaria, Falciparum / Q000235:genetics / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology
chemical_list: D006444:Hemoglobin C