- Title
- Urotensin-II system in genetic control of blood pressure and renal function
- Creator
- Debiec, Radoslaw; Christofidou, Paraskevi; Denniff, Matthew; Bloomer, Lisa; Bogdanski, Pawel; Wojnar, Lukasz; Musialik, Katarzyna; Charchar, Fadi; Thompson, John; Waterworth, Dawn; Song, Kijoung; Vollenweider, Peter; Waeber, Gerard; Zukowska-Szczechowska, Ewa; Samani, Nilesh; Lambert, David; Tomaszewski, Maciej
- Date
- 2013
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/66343
- Identifier
- vital:5740
- Identifier
- ISSN:1932-6203
- 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 familybased 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. © 2013 Debiec et al.
- Relation
- PLoS ONE Vol. 8, no. 12 (2013), p.
- Rights
- Copyright PLOS one
- Rights
- Open Access
- Rights
- This metadata is freely available under a CCO license
- Subject
- MD Multidisciplinary; Alleles; Blood pressure; Evolutionary genetics; Gene expression; Human genetics; Hypertension; Kidneys; Primates
- Full Text
- Reviewed
- Hits: 10031
- Visitors: 9832
- Downloads: 185
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | Published Version | 260 KB | Adobe Acrobat PDF | View Details Download |