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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., (Copyright © 2015 by the American Society of Nephrology.)

Urotensin-II controls ion/water homeostasis in fish and vascular tone in rodents. We hypothesised that common genetic variants in urotensin-II pathway genes are associated with human blood pressure or renal function. We performed family-based analysis of association between blood pressure, glomerular filtration and genes of the urotensin-II pathway (urotensin-II, urotensin-II related peptide, urotensin-II receptor) saturated with 28 tagging single nucleotide polymorphisms in 2024 individuals from 520 families; followed by an independent replication in 420 families and 7545 unrelated subjects. The expression studies of the urotensin-II pathway were carried out in 97 human kidneys. Phylogenetic evolutionary analysis was conducted in 17 vertebrate species. One single nucleotide polymorphism (rs531485 in urotensin-II gene) was associated with adjusted estimated glomerular filtration rate in the discovery cohort (p = 0.0005). It showed no association with estimated glomerular filtration rate in the combined replication resource of 8724 subjects from 6 populations. Expression of urotensin-II and its receptor showed strong linear correlation (r = 0.86, p<0.0001). There was no difference in renal expression of urotensin-II system between hypertensive and normotensive subjects. Evolutionary analysis revealed accumulation of mutations in urotensin-II since the divergence of primates and weaker conservation of urotensin-II receptor in primates than in lower vertebrates. Our data suggest that urotensin-II system genes are unlikely to play a major role in genetic control of human blood pressure or renal function. The signatures of evolutionary forces acting on urotensin-II system indicate that it may have evolved towards loss of function since the divergence of primates.

Green tea (GT) consumption is known to be associated with enhanced cardiovascular and metabolic health. The purpose of this study is to examine the hypothesis that supplementation with GT alters insulin resistance and associated cardiovascular risk factors in obese, hypertensive patients. In a double-blind, placebo-controlled trial, 56 obese, hypertensive subjects were randomized to receive a daily supplement of 1 capsule that contained either 379 mg of GT extract (GTE) or a matching placebo, for 3 months. At baseline and after 3 months of treatment, the anthropometric parameters, blood pressure, plasma lipid levels, glucose levels, creatinine levels, tumor necrosis factor α levels, C-reactive protein levels, total antioxidant status, and insulin levels were assessed. Insulin resistance was evaluated according to the homeostasis model assessment-insulin resistance protocol. After 3 months of supplementation, both systolic and diastolic blood pressures had significantly decreased in the GTE group as compared with the placebo group (P < .01). Considerable (P < .01) reductions in fasting serum glucose and insulin levels and insulin resistance were observed in the GTE group when compared with the placebo group. Serum tumor necrosis factor α and C-reactive protein were significantly lower, whereas total antioxidant status increased in the GTE group compared with the placebo (P < .05). Supplementation also contributed to significant (P < .05) decreases in the total and low-density lipoprotein cholesterol and triglycerides, but an increase in high-density lipoprotein cholesterol. In conclusion, daily supplementation with 379 mg of GTE favorably influences blood pressure, insulin resistance, inflammation and oxidative stress, and lipid profile in patients with obesity-related hypertension., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Progranulin and family with sequence similarity 19, member A5 (FAM19A5) protein are adipokines with growing importance in the context of metabolic diseases. The study aimed to determine the serum concentration of progranulin and FAM19A5 in people with metabolic syndrome (MS) compared to those without MS. The concentration of progranulin and FAM19A5 was determined in 45 people with MS (group A) and in 35 healthy people without MS (group B). Body composition analysis, blood pressure, blood oxygen saturation and anthropometric measurements were performed. There were no differences in the blood levels of progranulin and FAM19A5 between the groups. In group A, the level of progranulin was 29.25±36.92 pg/ml and in group B it was 46.00±60.12pg/ml (p=0.2693). The level of FAM19A5 was 163.16±55.11 pg/ml and 197.57±112.89 pg/ml (p=0.1341) in subjects with and without metabolic syndrome, respectively. In group A, there was a correlation between FAM19A5 and diastolic blood pressure (DBP) (R= –0.40) and high-density lipoprotein (HDL) level (R= –0.37). In group B, correlations were found between progranulin and waist circumference (R= –0.43) and progranulin and triglyceride (TG) levels (R= –0.42). Both groups together showed correlations between progranulin level and body mass index (R= –0.24), HDL (R=0.25) and TG levels (R= –0.25) and between FAM19A5 level and DBP (R= –0.34). In conclusion, patients with and without MS do not differ in the range of progranulin and FAM19A5 serum levels. In patients with MS, elevated FAM19A5 serum levels may be an indicator of dyslipidaemia development. FAM19A5 appears to be a better predictor of MS than progranulin. [ABSTRACT FROM AUTHOR]