Clinical ResearchPathway Analysis Shows Association between FGFBP1 and HypertensionTomaszewski, Maciej*,†; Charchar, Fadi J.‡; Nelson, Christopher P.*; Barnes, Timothy*; Denniff, Matthew*; Kaiser, Michael*; Debiec, Radoslaw*; Christofidou, Paraskevi*; Rafelt, Suzanne*; van der Harst, Pim*,§; Wang, William Y. S.*,‖; Maric, Christine¶; Zukowska-Szczechowska, Ewa**; Samani, Nilesh J.*,† Author Information *Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom; †Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, United Kingdom; ‡School of Science and Engineering, University of Ballarat, Ballarat, Australia; §Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; ‖School of Medicine, University of Queensland, Brisbane, Australia; ¶Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi; and **Department of Internal Medicine, Diabetology and Nephrology, Medical University of Silesia, Zabrze, Poland Correspondence: Dr. Maciej Tomaszewski, Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences Wing, Glenfield Hospital, Leicester LE3 9QP, UK. Phone: 44-116-256-3019; Fax: 44-116-287-5792; E-mail: [email protected] Received August 12, 2010 Accepted December 7, 2010 Journal of the American Society of Nephrology 22(5):p 947-955, May 2011. | DOI: 10.1681/ASN.2010080829 Buy Metrics Abstract 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. Copyright © 2011 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.