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Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans.
J Clin Endocrinol Metab. 2011 Nov; 96(11):3541-9.JC

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.

Authors+Show Affiliations

Department of Medicine, Indiana University School of Medicine, 541 North Clinical Drive, CL 459, Indianapolis, Indiana 46202, USA. eimel@iupui.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21880793

Citation

Imel, Erik A., et al. "Iron Modifies Plasma FGF23 Differently in Autosomal Dominant Hypophosphatemic Rickets and Healthy Humans." The Journal of Clinical Endocrinology and Metabolism, vol. 96, no. 11, 2011, pp. 3541-9.
Imel EA, Peacock M, Gray AK, et al. Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans. J Clin Endocrinol Metab. 2011;96(11):3541-9.
Imel, E. A., Peacock, M., Gray, A. K., Padgett, L. R., Hui, S. L., & Econs, M. J. (2011). Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans. The Journal of Clinical Endocrinology and Metabolism, 96(11), 3541-9. https://doi.org/10.1210/jc.2011-1239
Imel EA, et al. Iron Modifies Plasma FGF23 Differently in Autosomal Dominant Hypophosphatemic Rickets and Healthy Humans. J Clin Endocrinol Metab. 2011;96(11):3541-9. PubMed PMID: 21880793.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans. AU - Imel,Erik A, AU - Peacock,Munro, AU - Gray,Amie K, AU - Padgett,Leah R, AU - Hui,Siu L, AU - Econs,Michael J, Y1 - 2011/08/31/ PY - 2011/9/2/entrez PY - 2011/9/2/pubmed PY - 2011/12/24/medline SP - 3541 EP - 9 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 96 IS - 11 N2 - 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. SN - 1945-7197 UR - https://www.unboundmedicine.com/medline/citation/21880793/Iron_modifies_plasma_FGF23_differently_in_autosomal_dominant_hypophosphatemic_rickets_and_healthy_humans_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2011-1239 DB - PRIME DP - Unbound Medicine ER -