title: Ferroportin (SLC40A1) Q248H mutation is associated with lower circulating plasma tumor necrosis factor-alpha and macrophage migration inhibitory factor concentrations in African children.
abstract: 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.
authors.affiliation: Department of Chemical Pathology, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe. kasvosve@yahoo.com
authors.forename: Ishmael
authors.initials: I
authors.lastname: Kasvosve
authors.forename: Zufan
authors.initials: Z
authors.lastname: Debebe
authors.forename: Sergei
authors.initials: S
authors.lastname: Nekhai
authors.forename: Victor R
authors.initials: VR
authors.lastname: Gordeuk
mesh_terms: 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
chemical_list: D027682:Cation Transport Proteins; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha; D000098742:Ferroportin
references.citation: J Immunol. 2008 Aug 15;181(4):2723-31
references.pmid: 18684963
references.citation: Cytokine. 2004 Apr 21;26(2):73-81
references.pmid: 15050607
references.citation: Surgery. 1988 Aug;104(2):280-6
references.pmid: 2456628
references.citation: Proc Natl Acad Sci U S A. 1990 Dec;87(24):9769-73
references.pmid: 2263628
references.citation: Blood Cells Mol Dis. 2004 Jan-Feb;32(1):131-8
references.pmid: 14757427
references.citation: Blood. 2005 May 15;105(10):4096-102
references.pmid: 15692071
references.citation: J Immunol. 1997 Jan 1;158(1):420-5
references.pmid: 8977218
references.citation: Blood. 2003 May 15;101(10):4148-54
references.pmid: 12522003
references.citation: Eur Cytokine Netw. 1994 Jul-Aug;5(4):401-4
references.pmid: 7841356
references.citation: Blood Cells Mol Dis. 2003 Nov-Dec;31(3):305-9
references.pmid: 14636643
references.citation: Annu Rev Nutr. 2006;26:323-42
references.pmid: 16848710
references.citation: J Membr Biol. 2005 Jul;206(1):3-7
references.pmid: 16440176
references.citation: Nature. 2000 Feb 17;403(6771):776-81
references.pmid: 10693807
references.citation: J Biol Chem. 1988 Sep 5;263(25):12638-44
references.pmid: 3410854
references.citation: Am J Trop Med Hyg. 1996 Oct;55(4):399-404
references.pmid: 8916795
references.citation: Am J Clin Nutr. 1980 Jan;33(1):86-118
references.pmid: 6986756
references.citation: Blood. 2005 Aug 1;106(3):1092-7
references.pmid: 15831700
references.citation: J Biol Chem. 2000 Jun 30;275(26):19906-12
references.pmid: 10747949
references.citation: J Biol Chem. 2003 May 16;278(20):17646-54
references.pmid: 12637578
references.citation: J Clin Invest. 2007 Jul;117(7):1755-8
references.pmid: 17607352
references.citation: J Biochem. 1998 Apr;123(4):733-9
references.pmid: 9538268
references.citation: J Gastroenterol Hepatol. 2005 Dec;20(12):1855-8
references.pmid: 16336444
references.citation: J Biol Response Mod. 1987 Oct;6(5):484-8
references.pmid: 3681344
references.citation: Clin Exp Immunol. 2001 Feb;123(2):309-14
references.pmid: 11207663
references.citation: Biochem J. 2006 Jul 1;397(1):61-7
references.pmid: 16566752
references.citation: Blood. 2005 Dec 1;106(12):3979-84
references.pmid: 16081696
references.citation: Blood. 1996 Mar 15;87(6):2525-37
references.pmid: 8630420
references.citation: Eur J Clin Invest. 2002 Mar;32 Suppl 1:70-8
references.pmid: 11886435
references.citation: Blood Cells Mol Dis. 2007 May-Jun;38(3):247-52
references.pmid: 17276706
references.citation: J Clin Invest. 2001 Aug;108(4):619-23
references.pmid: 11518736
references.citation: Clin Chim Acta. 2006 Sep;371(1-2):130-6
references.pmid: 16603144
references.citation: Am J Physiol. 1997 Jun;272(6 Pt 1):G1355-64
references.pmid: 9227470
references.citation: N Engl J Med. 2004 Jun 3;350(23):2383-97
references.pmid: 15175440
references.citation: Am J Physiol Gastrointest Liver Physiol. 2008 Sep;295(3):G512-21
references.pmid: 18599584
references.citation: J Clin Invest. 2002 Oct;110(7):1037-44
references.pmid: 12370282
references.citation: Am J Physiol Gastrointest Liver Physiol. 2002 Sep;283(3):G719-26
references.pmid: 12181188
references.citation: Lab Invest. 1989 Sep;61(3):319-22
references.pmid: 2788773
references.citation: Annu Rev Immunol. 1992;10:411-52
references.pmid: 1590993
references.citation: Blood. 1992 Apr 1;79(7):1855-60
references.pmid: 1558977
references.citation: Cell. 2002 Apr;109 Suppl:S81-96
references.pmid: 11983155
references.citation: Br J Haematol. 1960 Jan;6:43-55
references.pmid: 14427868
references.citation: J Immunol. 1990 Dec 15;145(12):4154-66
references.pmid: 2258613
references.citation: Clin Immunol. 2004 Dec;113(3):340-4
references.pmid: 15507399
references.citation: Science. 2004 Dec 17;306(5704):2090-3
references.pmid: 15514116
references.citation: Am J Clin Nutr. 2005 Nov;82(5):1102-6
references.pmid: 16280445
references.citation: Am J Clin Nutr. 1987 Aug;46(2):346-52
references.pmid: 3497573
references.citation: Blood Cells Mol Dis. 2003 Nov-Dec;31(3):299-304
references.pmid: 14636642
references.citation: Mol Cell. 2000 Feb;5(2):299-309
references.pmid: 10882071
references.citation: Am J Physiol. 1999 Dec;277(6):G1240-50
references.pmid: 10600822