Dataset Information

Neuropeptide Y(1) Receptor NPY1R discovery of naturally occurring human genetic variants governing gene expression in cella as well as pleiotropic effects on autonomic activity and blood pressure in vivo.

ABSTRACT:

Objectives

We asked whether naturally occurring genetic variation at the human NPY1R locus alters autonomic traits that might predispose individuals to cardiovascular disease.

Background

Neuropeptide Y (NPY) interacts with the Y(1) receptor, NPY1R, to control adrenergic activity and blood pressure (BP).

Methods

We searched for polymorphism at NPY1R by systematic resequencing in ethnically diverse people. There were 376 twins/siblings who were evaluated for heritable autonomic traits: baroreflex function and pressor response to environmental stress.

Results

The common NPY1R variant A+1050G in the 3'-untranslated region (3'-UTR) predicted baroreceptor slope (p = 0.014-0.047) and BP change to cold stress (p = 0.0091-0.016), with minor allele homozygotes displaying blunted slope and exaggerated pressor response. In 936 individuals with the most extreme BPs in the population, not only 3'-UTR A+1050G (p = 1.2 x 10(-4)) but also promoter A-585T (p = 0.001) affected both systolic BP and diastolic BP, in interactive fashion (p = 0.007), with combined homozygotes showing the highest diastolic BP (>20 mm Hg). The 3'-UTR variant +1050G decreased expression of a transfected luciferase reporter/NPY1R 3'-UTR plasmid; promoter variant A-585 also decreased expression of an NPY1R promoter/luciferase reporter. Thus, alleles that increased BP in vivo (3'-UTR +1050G, promoter A-585) also decreased NPY1R expression in cella. Computational alignment showed that A+1050G disrupted a microRNA motif.

Conclusions

Our results indicate that naturally occurring genetic variation at the NPY1R locus has implications for heritable autonomic control of the circulation, and ultimately, for systemic hypertension. The findings suggest novel pathophysiological links between the NPY1R locus, autonomic activity, and blood pressure, and suggest new strategies to approach the mechanism, diagnosis, and treatment of systemic hypertension.

SUBMITTER: Wang L

PROVIDER: S-EPMC2792636 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Publications

Neuropeptide Y(1) Receptor NPY1R discovery of naturally occurring human genetic variants governing gene expression in cella as well as pleiotropic effects on autonomic activity and blood pressure in vivo.

Wang Lei L Rao Fangwen F Zhang Kuixing K Mahata Manjula M Rodriguez-Flores Juan L JL Fung Maple M MM Waalen Jill J Cockburn Myles G MG Hamilton Bruce A BA Mahata Sushil K SK O'Connor Daniel T DT

Journal of the American College of Cardiology 20090901 10

<h4>Objectives</h4>We asked whether naturally occurring genetic variation at the human NPY1R locus alters autonomic traits that might predispose individuals to cardiovascular disease.<h4>Background</h4>Neuropeptide Y (NPY) interacts with the Y(1) receptor, NPY1R, to control adrenergic activity and blood pressure (BP).<h4>Methods</h4>We searched for polymorphism at NPY1R by systematic resequencing in ethnically diverse people. There were 376 twins/siblings who were evaluated for heritable autonom ...[more]

PMID: 19712806

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Dataset Information

Neuropeptide Y(1) Receptor NPY1R discovery of naturally occurring human genetic variants governing gene expression in cella as well as pleiotropic effects on autonomic activity and blood pressure in vivo.

Objectives

Background

Methods

Results

Conclusions

Publications

Neuropeptide Y(1) Receptor NPY1R discovery of naturally occurring human genetic variants governing gene expression in cella as well as pleiotropic effects on autonomic activity and blood pressure in vivo.

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