Endocrine Abstracts (2007) 13 OC31

Evidence for associations between fibroblast growth factor 1 gene and human hypertension

M Tomaszewski


University of Glasgow, Glasgow, United Kingdom.


Fibroblast growth factor 1 gene (FGF1) is located within the blood pressure quantitative trait locus on human chromosome 5 and encodes a multifunctional regulator of cardiovascular function and structure. To dissect associations between blood pressure and this positional candidate gene 51 FGF1 single nucleotide polymorphisms identified either in sequencing or/and public databases were genotyped in 629 individuals from 207 white hypertensive families. Linkage disequilibrium mapping based on the genotyped markers showed 3 independent FGF1 haploblocks that did not overlap with the adjacent chromosomal regions. Single locus and haplotype family-based analysis revealed the association between systolic blood pressure and FGF1 that was driven by two single genetic variants in haploblock 1 and 2 of the gene (P=0.0036 and P=0.0038, respectively). Compared with the normotensive controls, hypertensive individuals exhibited approximately 1.7-fold higher expression of FGF1 in renal tissue at both mRNA and protein level. Immunohistochemical analysis showed that FGF1 up-regulation occurred exclusively in mesangial and endothelial cells of the glomeruli. These data clearly show that association between human hypertension and FGF1 may be mediated by its up-regulation within the renal cortex.

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