Genetic Studies of Fibroblast Growth Factor 23 and Its Relationship to Metabolic Phenotypes

Fibroblast growth factor 23 (FGF23) is a new member of the FGF family. FGF23 is secreted by osteoblast when calcitriol is increased, serum phosphate is elevated, or parathyroid hormone level is high. FGF23 inhibits renal resorption of phosphates, inhibits the synthesis of calcitriol, and reduce parathyroid hormone levels. A rare gain-of-function mutation of FGF23 causes autosomal dominant hypophosphatemic rickets. Recently, FGF23 emerged to be involved in several other important physiological and pathological mechanisms such as inflammation, insulin resistance, proteinuria and left ventricular hypertrophy, and cardiovascular diseases. Previous study indicates that the individual variation of serum FGF23 is large. However, the genetic factors that determine serum FGF23 levels remained unknown. In this proposal, we expected to apply for the serum and the delinked clinical information, as well as whole genome sequence, and genome-wide SNP information in 5,000 participants from Taiwan Biobank. We proposed to 1. Investigate the association between serum FGF23 levels, body mass index, waist circumference, fasting glucose, cholesterol, triglycerides, blood pressure, liver function enzymes, glomerular filtration rate, uric acid, bone mass density, and metabolic syndrome. 2. Use single nucleotide polymorphism information retrieved from Taiwan Biobank to identify the genetic loci that determine serum FGF23 levels in 3,000 participants. The results will be further validated using additional 2,000 participants. 3. Identify rare genetic variants that regulate serum FGF23 levels suing delinked whole-genome sequence data retrieved from Taiwan Biobank. 4. Using human osteoblastoma cell line as a model to study the effect of the identified gene on the mRNA and protein expression of FGF23. This proposal would help further understanding the molecular mechanisms and functions of FGF23 and applying the findings for prevention or treatment of FGF23 related disorders.

Project ID:PC10608-1491
External Project ID:MOST106-2314-B182-043