Pubblicazione scientifica

Urotensin-II System in Genetic Control of Blood Pressure and Renal Function

FILONE TECNOLOGICO	TEMA
trasformazione e commercializzazione

RIASSUNTO

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.

DATA

Data di pubblicazione: 31/12/2013

AUTORI

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

ENTE DI AFFERENZA

DEPT CARDIOVASCULAR SCIENCES UNIV LEICESTER LEICESTER UK
DEPT INTERNAL MEDICINE METABOLIC DISORDERS & HYPERTENSION MEDICAL UNIV POZNAN POZNAN POLAND
DEPT UROLOGY & ONCOLOGICAL UROLOGY MEDICAL UNIV POZNAN POZNAN POLAND
SCHOOL OF SCIENCE & ENG UNIV BALLARAT BALLARAT AUSTRALIA
GLAXOSMITHKLINE PHILADELPHIA PENNSYLVANIA USA
DEPT MEDICINE CTR HOSPITALIER UNIV VAUDOIS LAUSANNE SWITZERLAND
DEPT INTERNAL MEDICINE DIABETOLOGY & NEPHROLOGY MEDICAL UNIV SILESIA ZABRZE POLAND
UNIV MARYLAND SCHOOL OF MEDICINE USA

RIVISTA

PLoS ONE, 8(12), e83137

IMPACT FACTOR

2,870

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