title: Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans.
abstract: BACKGROUND
  In autosomal dominant hypophosphatemic rickets (ADHR), fibroblast growth factor 23 (FGF23) resists cleavage, causing increased plasma FGF23 levels. The clinical phenotype includes variable onset during childhood or adulthood and waxing/waning of hypophosphatemia. Delayed onset after puberty in females suggests iron status may be important.
  
  
  OBJECTIVE
  Studies were performed to test the hypothesis that plasma C-terminal and intact FGF23 concentrations are related to serum iron concentrations in ADHR.
  
  
  METHODS
  Cross-sectional and longitudinal studies of ADHR and a cross-sectional study in healthy subjects were conducted at an academic medical center.
  
  
  METHODS
  Participants included 37 subjects with ADHR mutations from four kindreds and 158 healthy adult controls.
  
  
  METHODS
  The relationships of serum iron concentrations with plasma C-terminal and intact FGF23 concentrations were evaluated.
  
  
  RESULTS
  Serum phosphate and 1,25-dihydroxyvitamin D correlated negatively with C-terminal FGF23 and intact FGF23 in ADHR but not in controls. Serum iron was negatively correlated to both C-terminal FGF23 (r = -0.386; P < 0.05) and intact FGF23 (r = -0.602; P < 0.0001) in ADHR. However, control subjects also demonstrated a negative relationship of serum iron with C-terminal FGF23 (r = -0.276; P < 0.001) but no relationship with intact FGF23. Longitudinally in ADHR subjects, C-terminal FGF23 and intact FGF23 concentrations changed negatively with iron concentrations (P < 0.001 and P = 0.055, respectively), serum phosphate changed negatively with C-terminal FGF23 and intact FGF23 (P < 0.001), and there was a positive relationship between serum iron and phosphate (P < 0.001).
  
  
  CONCLUSIONS
  Low serum iron is associated with elevated FGF23 in ADHR. However, in controls, low serum iron was also associated with elevated C-terminal FGF23, but not intact FGF23, suggesting cleavage maintains homeostasis despite increased FGF23 expression.
authors: Department of Medicine, Indiana University School of Medicine, 541 North Clinical Drive, CL 459, Indianapolis, Indiana 46202, USA. eimel@iupui.edu
authors: Erik A
authors: EA
authors: Imel
authors: Munro
authors: M
authors: Peacock
authors: Amie K
authors: AK
authors: Gray
authors: Leah R
authors: LR
authors: Padgett
authors: Siu L
authors: SL
authors: Hui
authors: Michael J
authors: MJ
authors: Econs
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood* / Q000235:genetics; D006801:Humans; D017674:Hypophosphatemia / Q000235:genetics / Q000378:metabolism*; D007501:Iron / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012279:Rickets / Q000235:genetics / Q000378:metabolism*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: C000717427:FGF23 protein, human; D014807:Vitamin D; D005346:Fibroblast Growth Factors; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23; D007501:Iron