Document Detail


Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans.
MedLine Citation:
PMID:  21880793     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: 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.
DESIGN AND SETTING: Cross-sectional and longitudinal studies of ADHR and a cross-sectional study in healthy subjects were conducted at an academic medical center.
PARTICIPANTS: Participants included 37 subjects with ADHR mutations from four kindreds and 158 healthy adult controls.
MAIN OUTCOME MEASURE: 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:
Erik A Imel; Munro Peacock; Amie K Gray; Leah R Padgett; Siu L Hui; Michael J Econs
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-08-31
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  96     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-07     Completed Date:  2011-12-23     Revised Date:  2013-02-19    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3541-9     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, Indiana University School of Medicine, 541 North Clinical Drive, CL 459, Indianapolis, Indiana 46202, USA. eimel@iupui.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Cross-Sectional Studies
Female
Fibroblast Growth Factors / blood*,  genetics
Humans
Hypophosphatemia / genetics,  metabolism*
Iron / blood*
Male
Middle Aged
Mutation
Rickets / genetics,  metabolism*
Vitamin D / analogs & derivatives,  blood
Grant Support
ID/Acronym/Agency:
K23 AR057096/AR/NIAMS NIH HHS; K23AR057096/AR/NIAMS NIH HHS; L40 AR056526/AR/NIAMS NIH HHS; P01 AG18397/AG/NIA NIH HHS; R01 AR042228/AR/NIAMS NIH HHS; R01AR42228/AR/NIAMS NIH HHS; R21 AR061078-02/AR/NIAMS NIH HHS; UL1RR025761/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/fibroblast growth factor 23; 1406-16-2/Vitamin D; 62031-54-3/Fibroblast Growth Factors; 66772-14-3/1,25-dihydroxyvitamin D; 7439-89-6/Iron
Comments/Corrections

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