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Genome-Wide Association Study Implicates Atrial Natriuretic Peptide Rather Than B-Type Natriuretic Peptide in the Regulation of Blood Pressure in the General Population.

ABSTRACT: BACKGROUND:Cardiomyocytes secrete atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in response to mechanical stretching, making them useful clinical biomarkers of cardiac stress. Both human and animal studies indicate a role for ANP as a regulator of blood pressure with conflicting results for BNP. METHODS AND RESULTS:We used genome-wide association analysis (n=6296) to study the effects of genetic variants on circulating natriuretic peptide concentrations and compared the impact of natriuretic peptide-associated genetic variants on blood pressure (n=27?059). Eight independent genetic variants in 2 known (NPPA-NPPB and POC1B-GALNT4) and 1 novel locus (PPP3CC) associated with midregional proANP (MR-proANP), BNP, aminoterminal proBNP (NT-proBNP), or BNP:NT-proBNP ratio. The NPPA-NPPB locus containing the adjacent genes encoding ANP and BNP harbored 4 independent cis variants with effects specific to either midregional proANP or BNP and a rare missense single nucleotide polymorphism in NT-proBNP seriously altering its measurement. Variants near the calcineurin catalytic subunit gamma gene PPP3CC and the polypeptide N-acetylgalactosaminyltransferase 4 gene GALNT4 associated with BNP:NT-proBNP ratio but not with BNP or midregional proANP, suggesting effects on the post-translational regulation of proBNP. Out of the 8 individual variants, only those correlated with midregional proANP had a statistically significant albeit weak impact on blood pressure. The combined effect of these 3 single nucleotide polymorphisms also associated with hypertension risk (P=8.2×10-4). CONCLUSIONS:Common genetic differences affecting the circulating concentration of ANP associated with blood pressure, whereas those affecting BNP did not, highlighting the blood pressure-lowering effect of ANP in the general population.

SUBMITTER: Salo PP

PROVIDER: S-EPMC6072381 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Genome-Wide Association Study Implicates Atrial Natriuretic Peptide Rather Than B-Type Natriuretic Peptide in the Regulation of Blood Pressure in the General Population.

Salo Perttu P PP Havulinna Aki S AS Tukiainen Taru T Raitakari Olli O Lehtimäki Terho T Kähönen Mika M Kettunen Johannes J Männikkö Minna M Eriksson Johan G JG Jula Antti A Blankenberg Stefan S Zeller Tanja T Salomaa Veikko V Kristiansson Kati K Perola Markus M

Circulation. Cardiovascular genetics 20171201 6

<h4>Background</h4>Cardiomyocytes secrete atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in response to mechanical stretching, making them useful clinical biomarkers of cardiac stress. Both human and animal studies indicate a role for ANP as a regulator of blood pressure with conflicting results for BNP.<h4>Methods and results</h4>We used genome-wide association analysis (n=6296) to study the effects of genetic variants on circulating natriuretic peptide concentrations and ...[more]

PMID: 29237677

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Project description:New findingsWhat is the central question in this study? Atrial natriuretic peptide (ANP) is secreted in response to atrial wall distension and thus allows for evaluation, albeit indirect, of the central blood volume. Adrenaline has chronotropic and inotropic effects. We evaluated whether the chronotropic and inotropic effects of adrenaline were reflected in mid-regional proANP. What is the main finding and its importance? Central blood volume remained stable with infusion of adrenaline and yet mid-regional proANP increased. Thus, the chronotropic and inotropic state of the heart or adrenaline directly induces release of ANP variants from the myocytes.AbstractAtrial natriuretic peptide (ANP) has vasodilatory, natriuretic and diuretic properties. It is secreted in response to atrial wall distension and thereby provides an indirect evaluation of central blood volume (CBV). Adrenaline has chronotropic and inotropic effects that increase cardiac output. In the present study, we evaluated whether these effects were influenced by an increase in CBV and reflected in mid-regional proANP (MR-proANP) concentrations in the circulation, a stable proxy marker of bioactive ANP. Changes in CBV were evaluated by thoracic electrical admittance and haemodynamic variables monitored by pulse-contour analysis during two intervals with graded infusion of adrenaline. Adrenaline infusion increased heart rate (by 33 ± 18%) and stroke volume (by 6 ± 13%), hence cardiac output (by 42 ± 23%; all P < 0.05). The increase in cardiac output did not result from an increase in CBV, because thoracic electrical admittance remained stable (-3 ± 17%; P = 0.230). Serum MR-proANP concentrations were increased (by 26 ± 25%; P < 0.001) by adrenaline infusion and remained elevated 60 min postinfusion. We conclude that MR-proANP in the circulation is affected not only by CBV, but also by increased chronotropy/inotropy of the heart, or that adrenaline directly induces release of ANP variants from the myocytes.

Dataset Information

Genome-Wide Association Study Implicates Atrial Natriuretic Peptide Rather Than B-Type Natriuretic Peptide in the Regulation of Blood Pressure in the General Population.

Publications

Genome-Wide Association Study Implicates Atrial Natriuretic Peptide Rather Than B-Type Natriuretic Peptide in the Regulation of Blood Pressure in the General Population.

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