Genetic variants of <i>FGFR</i> 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 (<i>FGFRL1</i>) 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 <i>FGFR5</i> gene is related to giraffe-related characteristics (height, hypertension, and osteoporosis), and to assess the associations between genetic variants of the <i>FGFR</i> family and three phenotypes. An association study was performed to confirm the connections between hypertension, osteoporosis, and height and the <i>FGFR</i> family proteins (<i>FGFR1</i> to <i>FGFR5</i>). We identified a total of 192 genetic variants in the <i>FGFR</i> family and found six SNVs in the <i>FGFR2</i>, <i>FGFR3</i>, and <i>FGFR4</i> genes that were associated with two phenotypes simultaneously. Also, the <i>FGFR</i> family was found to be involved in calcium signalling, and three genetic variants of the <i>FGFR3</i> gene showed significant signals in the pituitary and hypothalamus. Taken together, these findings suggest that <i>FGFR</i> genes are associated with hypertension, height, and osteoporosis. In particular, the present study highlights the <i>FGFR3</i> gene, which influences two fundamental regulators of bone remodelling.高血压与骨质疏松症是最为常见的两类健康问题。近期一项研究指出，长颈鹿体内的成纤维细胞生长因子受体样蛋白1（FGFRL1）基因是最具潜力的候选基因，可对骨骼与心血管系统产生直接调控作用。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，并评估成纤维细胞生长因子受体（Fibroblast Growth Factor Receptor，FGFR）家族遗传变异与三种表型间的关联。本研究通过关联分析，确认了高血压、骨质疏松症、身高与FGFR家族蛋白（FGFR1至FGFR5）之间的联系。我们共在FGFR家族中鉴定出192个遗传变异，并发现FGFR2、FGFR3与FGFR4基因中的6个单核苷酸变异（Single Nucleotide Variants，SNVs）可同时与两种表型相关联。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。综上，本研究结果表明FGFR家族基因与高血压、身高及骨质疏松症存在关联。其中，FGFR3基因尤为值得关注，其可影响骨重塑的两大关键调控因子。