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J Clin Endocrinol Metab. 2011 Nov;96(11):3541-9. doi: 10.1210/jc.2011-1239. Epub 2011 Aug 31.

Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans.

Author information

1
Department of Medicine, Indiana University School of Medicine, 541 North Clinical Drive, CL 459, Indianapolis, Indiana 46202, USA. eimel@iupui.edu

Abstract

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.

PMID:
21880793
PMCID:
PMC3205884
DOI:
10.1210/jc.2011-1239
[Indexed for MEDLINE]
Free PMC Article
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