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J Am Soc Nephrol. 2011 May;22(5):947-55. doi: 10.1681/ASN.2010080829. Epub 2011 Mar 24.

Pathway analysis shows association between FGFBP1 and hypertension.

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  • 1Department of Cardiovascular Sciences, University of Leicester, Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester LE3 9QP, UK. mt142@le.ac.uk

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 by the American Society of Nephrology

PMID:
21436287
[PubMed - indexed for MEDLINE]
PMCID:
PMC3083316
Free PMC Article

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