Genetic variants of FGFR family associated with height, hypertension, and osteoporosis

Hypertension and osteoporosis are the most common types of health problems. A recent study suggested that the fibroblast growth factor receptor-like protein 1 (FGFRL1) gene in giraffes is the most promising candidate gene that may have direct effects on both the skeleton and the cardiovascular system. Our study purposed to replicate the finding that the FGFR5 gene is related to giraffe-related characteristics (height, hypertension, and osteoporosis), and to assess the associations between genetic variants of the FGFR family and three phenotypes. An association study was performed to confirm the connections between hypertension, osteoporosis, and height and the FGFR family proteins (FGFR1 to FGFR5). We identified a total of 192 genetic variants in the FGFR family and found six SNVs in the FGFR2, FGFR3, and FGFR4 genes that were associated with two phenotypes simultaneously. Also, the FGFR family was found to be involved in calcium signalling, and three genetic variants of the FGFR3 gene showed significant signals in the pituitary and hypothalamus. Taken together, these findings suggest that FGFR genes are associated with hypertension, height, and osteoporosis. In particular, the present study highlights the FGFR3 gene, which influences two fundamental regulators of bone remodelling.

高血压与骨质疏松症是临床最为常见的两类健康问题。近期一项研究表明，长颈鹿体内的成纤维细胞生长因子受体样蛋白1（fibroblast growth factor receptor-like protein 1, FGFRL1）基因是最具潜力的候选基因，其可能对骨骼系统与心血管系统均存在直接调控作用。本研究旨在验证“FGFR5基因与长颈鹿相关特征（身高、高血压及骨质疏松症）相关”这一发现，并评估FGFR家族基因的遗传变异与三种表型之间的关联。本研究通过关联分析，验证了高血压、骨质疏松症、身高与FGFR家族蛋白（FGFR1至FGFR5）之间的关联。本研究在FGFR家族中共鉴定出192个遗传变异，并发现FGFR2、FGFR3及FGFR4基因中的6个单核苷酸变异（single nucleotide variant, SNV）可同时与两种表型存在关联。此外，研究发现FGFR家族参与钙信号通路，且FGFR3基因的3个遗传变异在垂体与下丘脑组织中呈现显著关联信号。综合上述研究结果，FGFR基因与高血压、身高及骨质疏松症存在显著关联。尤为值得关注的是，本研究重点聚焦FGFR3基因，其可调控骨重塑的两种关键调节因子。