Iron Modifies Plasma FGF23 Differently in Autosomal Dominant Hypophosphatemic Rickets and Healthy Humans
Iron Modifies Plasma FGF23 Differently in Autosomal Dominant Hypophosphatemic Rickets and Healthy Humans
复制标题
DOI：
10.1210/jc.2011-1239
复制
发表时间：
2011-11-01
影响因子：
5.8
通讯作者：
Econs, Michael J.
中科院分区：
文献类型：
--
作者：
Imel, Erik A.;Peacock, Munro;Econs, Michael J.
内容：在常染色体显性遗传低磷血症性佝偻病（ADHR）中，成纤维细胞生长因子23（FGF 23）抵抗裂解，导致血浆FGF 23水平升高。临床表型包括在儿童期或成年期的可变发作和低磷血症的加重/减轻。青春期后女性延迟发病提示铁状态可能是重要的。目的：进行研究以检验血浆C-末端和完整FGF 23浓度与ADHR血清铁浓度相关的假设。设计和设置：ADHR的横断面和纵向研究以及健康受试者的横断面研究在学术医学中心进行。参与者：参与者包括37名来自4个kinetics和158名健康成人controls.Main结果测量ADHR突变的受试者：血清铁浓度与血浆C-末端和完整FGF 23浓度的关系进行了评估。ADHR组血清磷酸盐和1，25-二羟维生素D与C-末端FGF 23和完整FGF 23呈负相关，而对照组无相关性。ADHR患者血清铁与C端FGF 23（r = -0.386; P < 0.05）和完整FGF 23（r = -0.602; P < 0.0001）均呈负相关。然而，对照组也显示血清铁与C-末端FGF 23呈负相关（r = -0.276; P < 0.001），但与完整FGF 23无相关性。在ADHR受试者中，C-末端FGF 23和完整FGF 23浓度随铁浓度呈负向变化C-末端FGF 23和完整FGF 23的血清磷酸盐呈负性变化（P < 0.001和P = 0.055血清铁与血清磷呈正相关（P <0.001）。然而，在对照组中，低血清铁也与升高的C-末端FGF 23相关，但与完整的FGF 23无关，表明尽管FGF 23表达增加，但切割仍维持稳态。（临床内分泌代谢杂志96：3541-3549，2011）
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. (J Clin Endocrinol Metab 96: 3541-3549, 2011)