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Title: | Urotensin-II System in Genetic Control of Blood Pressure and Renal Function |
Authors: | Debiec, Radoslaw Christofidou, Paraskevi Denniff, Matthew Bloomer, Lisa D. Bogdanski, P. Wojnar, L. Musialik, K. Charchar, F. J. Thompson, John R. Waterworth, D. Song, K. Vollenweider, P. Waeber, G. Zukowska-Szczechowska, E. Samani, Nilesh J. Lambert, David Tomaszewski, Maciej |
First Published: | 31-Dec-2013 |
Publisher: | Public Library of Science |
Citation: | PLoS One, 2013, 8 (12), e83137 |
Abstract: | 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. |
DOI Link: | 10.1371/journal.pone.0083137 |
eISSN: | 1932-6203 |
Links: | http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083137 http://hdl.handle.net/2381/32717 |
Version: | Publisher Version |
Status: | Peer-reviewed |
Type: | Journal Article |
Rights: | Copyright © 2013 Debiec et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
Appears in Collections: | Published Articles, Dept. of Cardiovascular Sciences |
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Urotensin-II system in genetic control of blood pressure and renal function..pdf | Published (publisher PDF) | 421.58 kB | Adobe PDF | View/Open |
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