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Pathway analysis shows association between FGFBP1 and hypertension
Maciej Tomaszewski1, Fadi J Charchar, Christopher P Nelson
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
Journal of the American Society of Nephrology : JASN
|March 26, 2011
Summary
Genetic variants in fibroblast growth factor binding protein 1 (FGFBP1) are linked to hypertension. Increased FGFBP1 expression in the kidneys of hypertensive individuals further supports this association.
Area of Science:
- Genetics
- Cardiovascular Disease Research
- Molecular Biology
Background:
- Fibroblast growth factor 1 (FGF1) gene variants are associated with familial hypertension.
- Glomerular FGF1 upregulation correlates with hypertension.
- The FGF signaling pathway's role in hypertension requires further investigation.
Purpose of the Study:
- To investigate potential associations between genetic variants in the FGF signaling pathway and hypertension.
- To identify novel genetic factors contributing to hypertension susceptibility.
Main Methods:
- Genotyping of 79 single nucleotide polymorphisms (SNPs) across eight genes in the FGF signaling network in 629 subjects from 207 Polish hypertensive families.
- Family-based association analysis to assess allele transmission of SNPs.
- Validation of significant associations in an independent cohort of 807 unrelated Polish subjects.
- Quantitative analysis of renal FGFBP1 mRNA and protein expression in hypertensive versus normotensive individuals using RT-qPCR and Western blotting.
- Immunohistochemical analysis to localize FGFBP1 expression in renal tissues.
Main Results:
- A significant association was found between the rs16892645 polymorphism in the FGFBP1 gene and hypertension in family-based analysis (P=0.005).
- This association was independently validated in a separate cohort.
- Hypertensive subjects exhibited significantly higher renal FGFBP1 mRNA (1.5-fold, P=0.04) and protein (1.4-fold, P=0.001) expression compared to normotensive controls.
- Hypertension-related FGFBP1 upregulation was predominantly observed in the glomerulus and juxtaglomerular space.
Conclusions:
- The gene encoding FGF binding protein 1 (FGFBP1) is associated with hypertension.
- Elevated FGFBP1 expression in the kidneys, particularly in the glomerulus, is linked to hypertension.
- Systematic analysis of signaling pathways is a valuable strategy for uncovering novel genetic associations with complex diseases like hypertension.
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