Phosphate is an essential mineral for

skeletal mineralization, cellular energy maintenance and for buffering blood pH levels, but high plasma phosphate levels may be a risk for soft tissue calcification [6]. Phosphate is mainly bound to hydroxyapatite in bone and to intracellular components, and only approximately 1% circulates in the blood. The circulating phosphate concentration is regulated by FGF23, 1,25(OH)2D and PTH levels [1]. The significance of FGF23 in the pathogenesis of hypophosphatemic disorders was unveiled when FGF23 was discovered as the causative gene behind autosomal dominant hypophosphatemic rickets (ADHR), and tumor-induced phosphate wasting was associated with increased FGF23 synthesis. High FGF23 in these diseases leads to selleck compound excessive urinary phosphate excretion, inappropriately low 1,25(OH)2D and osteomalacia [5], [7] and [8]. FGF23 is normally PD0325901 mw inactivated by enzymatic cleavage, but FGF23 mutations in ADHR render the protein’s cleavage site resistant to degradation, thereby elevating circulating FGF23 [9] and [10]. In tumor-induced osteomalacia the tumor itself produces excess FGF23 and hypophosphatemia can be reversed by tumor removal [5]. A functional allelic variant rs7955866 (c.716C>T, p.T239M) in FGF23 has recently been linked to renal phosphate

leak in calcium nephrolithiasis [11]. FGF23716Tsubjects had lower plasma phosphate (P-Pi) and reduced renal tubular phosphate reabsorption compared with FGF23716C subjects. In addition, the p.T239M change increased FGF23 secretion and induced a higher

activation of the FGF receptor/ERK pathway compared to FGF23239T [11]. The impact of FGF23 gene variation on healthy populations has received little attention in research. The aim of this study was to explore genetic variations in the FGF23 gene and to study whether the gene variants associate with biochemical parameters of phosphate and calcium homeostasis and with bone outcomes (measured with DXA and pQCT) in healthy children and adolescents. A total of 183 children and adolescents, 110 girls (median age 13.3, range 7.4–18.8 years) and 73 boys (median age 12.6, range 7.7–18.1 years), were included in this school-based Hydroxychloroquine cross-sectional study in the capital region of Helsinki, in southern Finland (latitude 61°). The primary aim of the original study was to evaluate skeletal health in relation to vitamin D status during childhood and puberty; the secondary aim was to explore FGF23 gene variation and its role in bone health and mineral metabolism. The original cohort included 195 subjects [12] who were recruited from one primary and one secondary school; DNA was obtained for 183 of these subjects (94% of the original cohort), who were included in the present study.