Journal
BONE
Volume 71, Issue -, Pages 124-130Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2014.10.013
Keywords
Phosphate; FGF23; PTH; Child; Adolescent; Bone morphometry
Categories
Funding
- Foundation for Pediatric Research, Finland
- Yrjo Jahnsson Foundation, Finland
- Ministry of Education, Finland
- Academy of Finland [250780, 277843]
- Helsinki University Central Hospital, Finland
- Sigrid Juselius Foundation, Finland
- Folkhalsan Research Foundation, Finland
- Swedish Research Council, Sweden [2013-2603]
- Academy of Finland (AKA) [277843, 250780, 250780] Funding Source: Academy of Finland (AKA)
- Novo Nordisk Fonden [NNF14OC0009813] Funding Source: researchfish
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Fibroblast growth factor 23 (FGF23), a bone-derived hormone, participates in the hormonal bone-parathyroid-kidney axis, which is modulated by PTH, 1,25-dihydroxyvitamin D, plasma phosphate (Pi), and diet Inappropriately high serum FGF23, seen in certain genetic and acquired disorders, results in urinary phosphate wasting and impaired bone mineralization. This study investigated the impact of FGF23 gene variation on phosphate homeostasis and bone health. The study included 183 children and adolescents (110 girls) aged 7-19 years (median 13.2 years). Urine and blood parameters of calcium and phosphate homeostasis were analyzed. Bone characteristics were quantified by DXA and peripheral quantitative computed tomography (pQCT). Genetic FGF23 variation was assessed by direct sequencing of coding exons and flanking intronic regions. Nine FGF23 polymorphisms were detected; three of them were common: rs3832879 (c.212-37insC), rs7955866 (c.716C>T, p.T239M) and rs11063112 (c.2185A>T). Four different haplotypes and six different diplotypes were observed among these three polymorphisms. The variations in FGF23 significantly associated with plasma PTH and urinary Pi excretion, even after adjusting for relevant covariates. FGF23 variations independently associated with total hip BMD Z-score, but not with other bone outcomes. In instrument analysis, genetic variance in FGF23 was considered a weak instrument as it only induced small variations in circulating FGF23, PTH and Pi concentrations (F statistic less than 10). The observed associations between FGF23 variations and circulating PTH, and Pi excretion and total hip BMD Z-scores suggest that FGF23 polymorphisms may play a role in mineral homeostasis and bone metabolism. (C) 2014 The Authors. Published by Elsevier Inc.
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