Dataset Information

Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure.

ABSTRACT: The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P = 9.65 × 10(-5)) and diastolic BP (P = 7.61 × 10(-3)) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0 × 10(-3)). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, renin-angiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.

SUBMITTER: Tomaszewski M

PROVIDER: S-EPMC4657842 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure.

Tomaszewski Maciej M Eales James J Denniff Matthew M Myers Stephen S Chew Guat Siew GS Nelson Christopher P CP Christofidou Paraskevi P Desai Aishwarya A Büsst Cara C Wojnar Lukasz L Musialik Katarzyna K Jozwiak Jacek J Debiec Radoslaw R Dominiczak Anna F AF Navis Gerjan G van Gilst Wiek H WH van der Harst Pim P Samani Nilesh J NJ Harrap Stephen S Bogdanski Pawel P Zukowska-Szczechowska Ewa E Charchar Fadi J FJ

Journal of the American Society of Nephrology : JASN 20150427 12

The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P = 9.65 × 10(-5)) and diastolic BP (P = 7.61 × 10(-3)) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA i ...[more]

PMID: 25918036

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Project description:Importance:Cerebral microinfarcts are associated with increased risk of cognitive impairment and may have different risk factors than macroinfarcts. Subcortical microinfarcts are associated with declining blood pressure (BP) in elderly individuals. Objective:To investigate BP slopes as a risk factor for microinfarcts. Design, Setting, and Participants:From the population-based Mayo Clinic Study of Aging, 303 of 1158 individuals (26.2%) in this cohort study agreed to have an autopsy between November 1, 2004, and March 31, 2016. Cerebral microinfarcts were identified and classified as cortical or subcortical. Baseline and BP trajectories were compared for groups with no microinfarcts, subcortical microinfarcts, and cortical microinfarcts. A secondary logistic regression analysis was performed to assess associations of subcortical microinfarcts with midlife hypertension, as well as systolic and diastolic BP slopes. Main Outcomes and Measures:The presence of cerebral microinfarcts using BP slopes. Results:Of the 303 participants who underwent autopsy, 297 had antemortem BP measurements. Of these, 177 (59.6%) were men; mean (SD) age at death was 87.2 (5.3) years. The autopsied individuals and the group who died but were not autopsied were similar for all demographics except educational level with autopsied participants having a mean of 1 more year of education (1.06; 95% CI, 0.66-1.47 years; P?<?.01). Among 297 autopsied individuals with antemortem BP measurements, 47 (15.8%) had chronic microinfarcts; 30 (63.8%) of these participants were men. Thirty (63.8%) had cortical microinfarcts, 19 (40.4%) had subcortical microinfarcts, and 4 (8.5%) had only infratentorial microinfarcts. Participants with microinfarcts did not differ significantly on baseline systolic (mean difference, -1.48; 95% CI, -7.30 to 4.34; P?=?.62) and diastolic (mean difference of slope, -0.90; 95% CI, -3.93 to 2.13; P?=?.56) BP compared with those with no microinfarcts. However, participants with subcortical microinfarcts had a greater annual decline (negative slope) of systolic (mean difference of slope, 4.66; 95% CI, 0.13 to 9.19; P?=?.04) and diastolic (mean difference, 3.33; 95% CI, 0.61 to 6.06; P?=?.02) BP. Conclusions and Relevance:Subcortical microinfarcts were associated with declining BP. Future studies should investigate whether declining BP leads to subcortical microinfarcts or whether subcortical microinfarcts are a factor leading to declining BP.

Dataset Information

Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure.

Publications

Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure.

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