Human Molecular Genetics Advance Access originally published online on November 12, 2003
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Human Molecular Genetics, 2004, Vol. 13, No. 1 1-6
DOI: 10.1093/hmg/ddh002
© 2004 Oxford University Press
Hemoglobin C is associated with reduced Plasmodium falciparum parasitemia and low risk of mild malaria attack
1Université de la Méditerranée, Marseille, France and 2Université de Ouagadougou, Ouagadougou, Burkina Faso
Received May 28, 2003; Revised October 9, 2003; Accepted October 24, 2003
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 of 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 2 years. Hemoglobin C carriers had less frequent malaria attacks than AA individuals within the same age group (P=0.01). Since age correlated with malaria attack and parasitemia (P<0.0001), we took age into account 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.
* To whom correspondence should be addressed at: 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. Tel/Fax: +33 491803674; Email: rihet{at}luminy.univ-mrs.fr
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