Fibroblast growth factor 1 gene and hypertension - From the quantitative trait locus to positional analysis

Tomaszewski, Maciej, Charchar, Fadi J., Lynch, Mark D., Padmanabhan, Sandosh, Wang, William Y. S., Miller, William H., Grzeszczak, Wladyslaw, Maric, Christine, Zukowska-Szczechowska, Ewa and Dominiczak, Anna F. (2007) Fibroblast growth factor 1 gene and hypertension - From the quantitative trait locus to positional analysis. Circulation, 116 17: 1915-1924. doi:10.1161/CIRCULATIONAHA.107.710293

Author Tomaszewski, Maciej
Charchar, Fadi J.
Lynch, Mark D.
Padmanabhan, Sandosh
Wang, William Y. S.
Miller, William H.
Grzeszczak, Wladyslaw
Maric, Christine
Zukowska-Szczechowska, Ewa
Dominiczak, Anna F.
Title Fibroblast growth factor 1 gene and hypertension - From the quantitative trait locus to positional analysis
Journal name Circulation   Check publisher's open access policy
ISSN 0009-7322
Publication date 2007-10
Year available 2007
Sub-type Article (original research)
DOI 10.1161/CIRCULATIONAHA.107.710293
Volume 116
Issue 17
Start page 1915
End page 1924
Total pages 10
Place of publication Baltimore, MD United States
Publisher Lippincott Williams & Wilkins
Collection year 2008
Language eng
Formatted abstract
BACKGROUND - The distal portion of the long arm of chromosome 5 is linked to hypertension and contains functional candidate blood pressure-regulating genes.

- Tightening the grid of microsatellite markers under this quantitative trait locus in the Silesian Hypertension Study (629 individuals from 207 Polish hypertensive families) provided enhanced support for linkage of this region to blood pressure (maximal Z=3.51, P=0.0002). The fine mapping, comparative genomics, and functional prioritization identified fibroblast growth factor 1 gene (FGF1) as the positional candidate. Linkage disequilibrium mapping based on 51 single nucleotide polymorphisms spanning the locus showed no overlap between 3 independent haploblocks of FGF1 and the adjacent extragenic chromosomal regions. Single and multilocus family-based analysis revealed that genetic variation within FGF1 haploblock 1 was associated with hypertension and identified a common intronic single nucleotide polymorphism, rs152524, as the major driver of this association (P=0.0026). Real-time quantitative polymerase chain reaction and Western blotting analysis of renal tissue obtained from subjects undergoing unilateral nephrectomy showed an increase in both mRNA and protein FGF1 expression in hypertensive patients compared with normotensive controls. Renal immunohistochemistry revealed that FGF1 was expressed exclusively within the glomerular endothelial and mesangial cells.

CONCLUSIONS - Our data demonstrate that genetic variation within FGF1 cosegregates with elevated blood pressure in hypertensive families and that this association is likely to be mediated by upregulation of renal FGF1 expression. The results of our study will need to be replicated in other cohorts.
Keyword Genetics
Growth substances
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Centre for Advanced Imaging Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 18 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 21 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 17 May 2013, 19:17:06 EST by System User on behalf of Centre for Advanced Imaging