Haptoglobin levels are associated with haptoglobin genotype and α+-thalassemia in a malaria-endemic area

Haptoglobin (Hp) is an acute phase protein that removes free hemoglobin (Hb) released during hemolysis. Hp has also been shown to be toxic for malaria parasites. alpha(+)-Thalassemia is a hemoglobinopathy that results in subclinical hemolytic anemia. alpha(+)-Thassemia homozygosity confers protection against severe malarial disease by an as yet unidentified mechanism. Hp levels were measured in a serial cross-sectional survey of children in Madang Province, Papua New Guinea (PNG). Hp levels were related to age, Hp genotype, Hb levels, parasitemia, splenomegaly, and alpha(+)-thalassemia genotype. Surprisingly, children who were homozygous for alpha(+)-thalassemia had significantly higher levels of Hp than did heterozygotes, after controlling for relevant confounders. We suggest that this is the result of either reduced mean cell Hb associated with alpha(+)-thalassemia homozygosity or an elevated IL-6-dependent acute phase response.