Ferroportin (SLC40A1) Q248H mutation is associated with lower circulating plasma tumor necrosis factor-alpha and macrophage migration inhibitory factor concentrations in African children.
BACKGROUND
Iron deficiency and the Q248H mutation in the gene, SLC40A1, that encodes for the cellular iron exporter, ferroportin, are both common in African children. The iron status of macrophages influences the pro-inflammatory response of these cells. We hypothesized that Q248H mutation may modify the inflammatory response by influencing iron levels within macrophages.


METHODS
The Q248H mutation and circulating concentrations of ferritin, C-reactive protein and selected pro-inflammatory cytokines (interleukin-12, interferon-gamma, TNF-alpha, and macrophage migration inhibitory factor) and anti-inflammatory cytokines (interleukin-4 and interleukin-10) were measured in 69 pre-school children recruited from well-child clinics in Harare, Zimbabwe.


RESULTS
In multivariate analysis, both ferroportin Q248H and ferritin <10ug/L were associated with significantly lower circulating concentrations of tumor necrosis factor-alpha. Ferroportin Q248H but not low iron stores was associated with lower circulating macrophage migration inhibitory factor as well. Anti-inflammatory cytokine levels were not significantly associated with either ferroportin Q248H or iron status.


CONCLUSIONS
Ferroportin Q248H and low iron stores are both associated with lower circulating tumor necrosis factor-alpha, while only ferroportin Q248H is associated with lower circulating macrophage migration inhibitory factor. Whether the reduced production of tumor necrosis factor-alpha observed in ferroportin Q248H heterozygotes may be of significance in anemia of chronic disease is yet to be determined.
Kasvosve
Ishmael
I
Department of Chemical Pathology, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe. kasvosve@yahoo.com
Debebe
Zufan
Z
Nekhai
Sergei
S
Gordeuk
Victor R
VR
D000349:Africa; D027682:Cation Transport Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood*; D015999:Multivariate Analysis; D009154:Mutation; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D000098742:Ferroportin
D027682:Cation Transport Proteins; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha; D000098742:Ferroportin
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