Details

Autor(en) / Beteiligte

• Debiec, Radoslaw
• Christofidou, Paraskevi
• Denniff, Matthew
• Bloomer, Lisa D
• Bogdanski, Pawel
• Wojnar, Lukasz
• Musialik, Katarzyna
• Charchar, Fadi J
• Thompson, John R
• Waterworth, Dawn
• Song, Kijoung
• Vollenweider, Peter
• Waeber, Gerard
• Zukowska-Szczechowska, Ewa
• Samani, Nilesh J
• Lambert, David
• Tomaszewski, Maciej
• Armando, Ines

Titel

Urotensin-II system in genetic control of blood pressure and renal function

Ist Teil von

• PloS one, 2013-12, Vol.8 (12), p.e83137-e83137

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2013

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.