Human Molecular Genetics Advance Access published online on November 12, 2003
Human Molecular Genetics, doi:10.1093/hmg/ddh002
© 2003 by Oxford University Press
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1 Université de la Méditerranée, IFR48, Faculté de Pharmacie, Laboratoire d'Immunogénétique et de Pharmacologie du Paludisme-EA 864, 27 Bd Jean Moulin 13385 Marseille Cedex 5, France
* To whom correspondence should be addressed. E-mail: rihet{at}luminy.univ-mrs.fr.
Article
Hemoglobin C is associated with reduced Plasmodium falciparum parasitemia and low risk of mild malaria attack
2 Université de la Méditerranée, Marseille, France
3 Université de Ouagadougou, Ouagadougou, Burkina Faso
Genetic predisposition to malaria has been shown by epidemiological, case-control, and linkage studies. In particular, case-control studies have recently shown association between hemoglobin C and resistance to severe malaria in Mali and to clinical malaria in Burkina Faso. In a longitudinal study on families living in an endemic area, we investigated whether hemoglobin C is associated with reduced Plasmodium falciparum parasitemia and low risk of mild malaria attack. We surveyed 256 individuals (71 parents and 185 sibs) from 53 families during two years. Hemoglobin C carriers had less frequently malaria attack than AA individuals within the same age group (P = 0.01). Since age correlated with malaria attack and parasitemia (P < 0.0001), we took into account age in association analyses. We performed combined linkage and association analyses, which avoid biases due to population structure. Using multi-allelic tests, we evidenced association between hemoglobin genotype and phenotypes related to malarial infection and disease (P < 0.001). We further analyzed individual hemoglobin alleles and detected negative association between hemoglobin C and malaria attack (P = 0.00013). Analyses that took into account confounding factors confirmed the negative association of hemoglobin C with malaria attack (P = 0.0074) and evidenced a negative correlation between hemoglobin C and parasitemia (P = 0.0009). These associations indicate that hemoglobin C reduces parasitemia and confers protection against mild malaria attack.
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