Hemoglobin C is associated with reduced Plasmodium falciparum parasitemia and low risk of mild malaria attack.
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.
Rihet
Pascal
P
Université de la Méditerranée, IFR48, Faculté de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France. rihet@luminy.univ-mrs.fr
Flori
Laurence
L
Tall
Francois
F
Traore
Alfred S
AS
Fumoux
Francis
F
D000293:Adolescent; D000367:Age Factors; D000818:Animals; D002050:Burkina Faso; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006444:Hemoglobin C / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000235:genetics*; D018512:Parasitemia / Q000235:genetics*; D010641:Phenotype; D010963:Plasmodium falciparum; D012307:Risk Factors; D035781:Siblings
D006444:Hemoglobin C