Abstract:
Background: The relation between subclinical hemoglobinopathies and concentrations of
the iron-regulatory hormone hepcidin is not well characterized.
Objective: We investigated the relation of hepcidin concentration with
hemoglobinopathies among young children in Kenya.
Methods: We quantified serum hepcidin and ferritin in 435 Kenyan children aged 14-20
mo in a subsample of the Water, Sanitation, and Handwashing (WASH) Benefits Trial.
Blood samples were genotyped for α+-thalassemia and for sickle cell disorder. Hepcidin
was compared across sickle cell and α+-thalassemia genotypes separately by using
generalized linear models, and children who were normozygous for both conditions were
also compared with those who had either of these conditions. In the association between
hepcidin and ferritin, we assessed effect modification by genotype.
Results: In this population, we found that 16.2% had sickle cell trait and 0.2% had sickle
cell disorder, whereas 40.0% were heterozygous for α+-thalassemia and 8.2% were
homozygous. Hepcidin concentration did not differ by genotype, but effect modification
was found by genotype in the association between hepcidin and ferritin (P < 0.1). Among
normozygous sickle cell children (HbAA), there was an association between hepcidin
and ferritin (β = 0.92; 95% CI: 0.72, 1.10). However, among those with sickle cell trait
(HbAS), the association was no longer significant (β = 0.31; 95% CI: -0.04, 0.66).
Similarly, among children who were normozygous (αα/αα) or heterozygous (-α/αα) for
α+-thalassemia, hepcidin and ferritin were significantly associated [β = 0.94 (95% CI:
0.68, 1.20) and β = 0.77 (95% CI: 0.51, 1.03), respectively]; however, in children who
were homozygous for α+-thalassemia (-α/-α), there was no longer a significant
association (β = 0.45; 95% CI: -0.10, 1.00).
Conclusion: Hepcidin was not associated with hemoglobin genotype, but there may be a
difference in the way hepcidin responds to iron status among those with either sickle cell
trait or homozygous α+-thalassemia in young Kenyan children. This trial was registered
at clinicaltrials.gov as NCT01704105.