The haptoglobin 2-2 genotype is associated with a reduced incidence of Plasmodium falciparum malaria in children on the coast of Kenya

Background. Haptoglobin ( Hp) genotype determines the efficiency of hemoglobin clearance after malaria-induced hemolysis and alters antioxidant and immune functions. The Hp(2) allele is thought to have spread under strong selection pressure, but it is unclear whether this is due to protection from malaria or other diseases. Methods. We monitored the incidence of febrile malaria and other childhood illnesses with regard to Hp genotype in a prospective cohort of 312 Kenyan children during 558.3 child-years of follow-up. We also conducted 7 cross-sectional surveys to determine the prevalence of Plasmodium falciparum parasitemia. Results. The Hp(2/2) genotype was associated with a 30% reduction in clinical malarial episodes (adjusted incidence rate ratio, 0.67; P = .008 for Hp(2/2) vs. Hp(1/1) and Hp(2/1) combined). Protection increased with age; there was no protection in the first 2 years of life, 30% protection at >= 2 years of age, and 50% protection from 4-10 years of age. Children with the Hp(1/1) genotype had a significantly lower rate of nonmalarial fever (P = .001). Conclusions. Balancing selection pressures may have influenced the spread of the Hp gene. Our observations suggest that the Hp(2) allele may have spread as a result of protection from malaria, and the Hp(1) allele may be sustained by protection from other infections.