University of Oulu

Salo, P., Havulinna, A., Tukiainen, T., Raitakari, O., Lehtimäki, T., Kähönen, M., Kettunen, J., Männikkö, M., Eriksson, J., Jula, A., Blankenberg, S., Zeller, T., Salomaa, V., Kristiansson, K., Perola, M. (2017) Genome-Wide Association Study Implicates Atrial Natriuretic Peptide Rather Than B-Type Natriuretic Peptide in the Regulation of Blood Pressure in the General Population. Circulation: Cardiovascular Genetics, 10 (6).

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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Author: Salo, Perttu P.; Havulinna, Aki S.; Tukiainen, Taru;
Format: article
Version: published version
Access: open
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Language: English
Published: Wolters Kluwer, 2017
Publish Date: 2021-02-26


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.

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Series: Circulation. Cardiovascular genetics
ISSN: 1942-325X
ISSN-E: 1942-3268
ISSN-L: 1942-325X
Volume: 10
Issue: 6
Article number: UNSP e001713
DOI: 10.1161/CIRCGENETICS.117.001713
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: This study was supported by Aarne Koskelo Foundation; the Academy of Finland grants 269517, 250207, 269517, 283045, 297338, 286284 (Dr Lehtimäki), 134309(Eye), 126925, 121584, 124282, 129378(Salve), 117787(Gendi), and 41071(Skidi); Biomedicum Helsinki Foundation; the Competitive State Research Financing of the Expert Responsibility area of Tampere, Turku; Kuopio University Hospital (grant X51001); the Diabetes Research Foundation of the Finnish Diabetes Association; Emil Aaltonen Foundation; the EU FP7 grants 313010 (BBMRI-LPC), 305280 (MIMOmics), and HZ2020 633589 (Ageing with Elegans); Finnish Cultural Foundation; Finnish Foundation for Cardiovascular Research; Ida Montin Foundation; Integrative Life Science Doctoral Program of the University of Helsinki; Juho Vainio Foundation; Paavo Nurmi Foundation; Signe and Ane Gyllenberg Foundation; the Social Insurance Institution of Finland, Tampere Tuberculosis Foundation; and Yrjö Jahnsson Foundation.
Academy of Finland Grant Number: 297338
Detailed Information: 297338 (Academy of Finland Funding decision)
Copyright information: © 2017 The Authors. Circulation: Cardiovascular Genetics is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.