title: Pathway analysis shows association between FGFBP1 and hypertension.
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.
authors: Department of Cardiovascular Sciences, University of Leicester, Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester LE3 9QP, UK. mt142@le.ac.uk
authors: Maciej
authors: M
authors: Tomaszewski
authors: Fadi J
authors: FJ
authors: Charchar
authors: Christopher P
authors: CP
authors: Nelson
authors: Timothy
authors: T
authors: Barnes
authors: Matthew
authors: M
authors: Denniff
authors: Michael
authors: M
authors: Kaiser
authors: Radoslaw
authors: R
authors: Debiec
authors: Paraskevi
authors: P
authors: Christofidou
authors: Suzanne
authors: S
authors: Rafelt
authors: Pim
authors: P
authors: van der Harst
authors: William Y S
authors: WY
authors: Wang
authors: Christine
authors: C
authors: Maric
authors: Ewa
authors: E
authors: Zukowska-Szczechowska
authors: Nilesh J
authors: NJ
authors: Samani
mesh_terms: D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016220:Fibroblast Growth Factor 1; C070699:FGFBP1 protein, human