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.