Comparative Analysis of Iron Homeostasis in Sub-Saharan African Children with Sickle Cell Disease and Their Unaffected Siblings

Abstract

Iron is an essential trace element subject to tight regulation to ensure adequate running of biological processes. In sub-Saharan Africa where hemoglobinopathies are common, iron homeostasis is likely to be impaired by these conditions. Here, we assessed and compared key serum proteins associated with iron metabolism between sub-Saharan African children with sickle cell disease (SCD) and their unaffected siblings. Complete blood counts and serum concentrations of four key proteins involved in iron regulation (ferritin, transferrin, sTfR, and hepcidin) were measured for 73 children with SCD and 68 healthy siblings in Benin, West Africa. We found significant differences in concentration of transferrin, sTfR, and ferritin between the two groups. Hepcidin concentrations were found at unusually high concentrations but did not differ among the two groups. We found a significant negative correlation between hepcidin levels and both MCH and MCV in the SCD group and report that sTfR concentrations show a correlation with MCV and MHC in opposite directions in the two groups. These results highlight the unusually high levels of hepcidin in the Beninese population and the patterns of differential iron homeostasis taking place under SCD status. These results lay the foundation for a systematic evaluation of the underlying mechanisms deregulating iron homeostasis in populations with SCD or high prevalence of iron deficiency.

Keywords: anemia; hepcidin; iron deficiency; iron homeostasis; red blood cell indices; serum iron proteins; sickle cell disease.

Figure 1

Comparisons of means and variances of the four iron serum proteins in the control and SCD groups. Right panel: the diamonds show the 95% confidence intervals and the horizontal black line shows the mean value across the entire set of individuals. Left panel: the densities show the distribution of each protein in the control and SCD groups.

Figure 2

Association of hepcidin and sTfR with MCV in the control and SCD groups. (A) Full multivariate models (control group, left panel, and SCD group, right panel). (B,C) Univariate models testing the association of each protein (control group, left panels, and SCD group, right panel). The red solid line shows the line of fit, the red dashed line represents the 95% confidence curves and the blue dashed line shows the horizontal mean reference that represents the null hypothesis.

Figure 3

Association of hepcidin and sTfR with MCH in the control and SCD groups. (A) Full multivariate models (control group, left panel, and SCD group, right panel). (B,C) Univariate models testing the association of each protein (control group, left panels, and SCD group, right panel). The red solid line shows the line of fit, the red dashed line represents the 95% confidence curves and the blue dashed line shows the horizontal mean reference that represents the null hypothesis.