Pathway analysis shows association between FGFBP1 and hypertension.
Pathway analysis shows association between FGFBP1 and hypertension.
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DOI：
10.1681/asn.2010080829
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发表时间：
2011-05
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通讯作者：
M. Tomaszewski;F. Charchar;C. Nelson;T. Barnes;M. Denniff;M. Kaiser;R. Debiec;P. Christofidou;S. Rafelt;P. van der Harst;William Y S Wang;C. Maric;E. Zukowska-szczechowska;N. Samani
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作者：
M. Tomaszewski;F. Charchar;C. Nelson;T. Barnes;M. Denniff;M. Kaiser;R. Debiec;P. Christofidou;S. Rafelt;P. van der Harst;William Y S Wang;C. Maric;E. Zukowska-szczechowska;N. Samani
编码成纤维细胞生长因子1（FGF1）的基因变异与高血压的家族易感性共分离，并且肾小球FGF1上调与高血压相关。为了研究FGF信号通路其他成员的变异是否也与高血压相关，我们对来自207个波兰高血压家族的629名受试者进行了基因分型，检测了该网络8个基因的79个单核苷酸多态性。以家族为基础的分析表明，父母传递的主要等位基因的rs16892645多态性的基因编码FGF结合蛋白1（FGFBP1）高血压子女比预期的机会（P=0.005）。807名无关的波兰受试者的独立队列验证了这种关联。此外，与血压正常的受试者相比，高血压受试者的肾脏FGFBP 1 mRNA和蛋白表达分别高出约1.5倍和1.4倍（P=0.04和P=0.001）。通过免疫组化，高血压相关的FGFBP 1上调在肾小球和肾小球间隙中最明显。总之，这些数据表明，FGFBP 1与高血压有关，并且对信号通路的系统分析可以确定以前未描述的遗传关联。
Variants in the gene encoding fibroblast growth factor 1 (FGF1) co-segregate with familial susceptibility to hypertension, and glomerular upregulation of FGF1 associates with hypertension. To investigate whether variants in other members of the FGF signaling pathway may also associate with hypertension, we genotyped 629 subjects from 207 Polish families with hypertension for 79 single nucleotide polymorphisms in eight genes of this network. Family-based analysis showed that parents transmitted the major allele of the rs16892645 polymorphism in the gene encoding FGF binding protein 1 (FGFBP1) to hypertensive offspring more frequently than expected by chance (P=0.005). An independent cohort of 807 unrelated Polish subjects validated this association. Furthermore, compared with normotensive subjects, hypertensive subjects had approximately 1.5- and 1.4-fold higher expression of renal FGFBP1 mRNA and protein (P=0.04 and P=0.001), respectively. By immunohistochemistry, hypertension-related upregulation of FGFBP1 was most apparent in the glomerulus and juxtaglomerular space. Taken together, these data suggest that FGFBP1 associates with hypertension and that systematic analysis of signaling pathways can identify previously undescribed genetic associations.