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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

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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; Havulinna, Aki S; Tukiainen, Taru; Raitakari, Olli; Lehtimäki, Terho; Kähönen, Mika; Kettunen, Johannes; Männikkö, Minna; Eriksson, Johan G; Jula, Antti; Blankenberg, Stefan; Zeller, Tanja; Salomaa, Veikko; Kristiansson, Kati; Perola, Markus.

In: CIRC-CARDIOVASC GENE, Vol. 10, No. 6, 12.2017.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Salo, PP, Havulinna, AS, Tukiainen, T, Raitakari, O, Lehtimäki, T, Kähönen, M, Kettunen, J, Männikkö, M, Eriksson, JG, 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', CIRC-CARDIOVASC GENE, vol. 10, no. 6. https://doi.org/10.1161/CIRCGENETICS.117.001713

APA

Salo, P. P., Havulinna, A. S., Tukiainen, T., Raitakari, O., Lehtimäki, T., Kähönen, M., Kettunen, J., Männikkö, M., Eriksson, J. G., 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. CIRC-CARDIOVASC GENE, 10(6). https://doi.org/10.1161/CIRCGENETICS.117.001713

Vancouver

Salo PP, Havulinna AS, Tukiainen T, Raitakari O, Lehtimäki T, Kähönen M et al. Genome-Wide Association Study Implicates Atrial Natriuretic Peptide Rather Than B-Type Natriuretic Peptide in the Regulation of Blood Pressure in the General Population. CIRC-CARDIOVASC GENE. 2017 Dec;10(6). https://doi.org/10.1161/CIRCGENETICS.117.001713

Bibtex

@article{ba5e22eca4cc40d8970143b961e77c1d,
title = "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.",
keywords = "Adult, Aged, Atrial Natriuretic Factor/blood, Blood Pressure/genetics, Cohort Studies, Female, Finland, Genetic Variation, Genome-Wide Association Study, Humans, Male, Middle Aged, Myocytes, Cardiac/metabolism, Natriuretic Peptide, Brain/blood",
author = "Salo, {Perttu P} and Havulinna, {Aki S} and Taru Tukiainen and Olli Raitakari and Terho Lehtim{\"a}ki and Mika K{\"a}h{\"o}nen and Johannes Kettunen and Minna M{\"a}nnikk{\"o} and Eriksson, {Johan G} and Antti Jula and Stefan Blankenberg and Tanja Zeller and Veikko Salomaa and Kati Kristiansson and Markus Perola",
note = "{\textcopyright} 2017 The Authors.",
year = "2017",
month = dec,
doi = "10.1161/CIRCGENETICS.117.001713",
language = "English",
volume = "10",
journal = "CIRC-CARDIOVASC GENE",
issn = "1942-325X",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

RIS

TY - JOUR

T1 - Genome-Wide Association Study Implicates Atrial Natriuretic Peptide Rather Than B-Type Natriuretic Peptide in the Regulation of Blood Pressure in the General Population

AU - Salo, Perttu P

AU - Havulinna, Aki S

AU - Tukiainen, Taru

AU - Raitakari, Olli

AU - Lehtimäki, Terho

AU - Kähönen, Mika

AU - Kettunen, Johannes

AU - Männikkö, Minna

AU - Eriksson, Johan G

AU - Jula, Antti

AU - Blankenberg, Stefan

AU - Zeller, Tanja

AU - Salomaa, Veikko

AU - Kristiansson, Kati

AU - Perola, Markus

N1 - © 2017 The Authors.

PY - 2017/12

Y1 - 2017/12

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Atrial Natriuretic Factor/blood

KW - Blood Pressure/genetics

KW - Cohort Studies

KW - Female

KW - Finland

KW - Genetic Variation

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Middle Aged

KW - Myocytes, Cardiac/metabolism

KW - Natriuretic Peptide, Brain/blood

U2 - 10.1161/CIRCGENETICS.117.001713

DO - 10.1161/CIRCGENETICS.117.001713

M3 - SCORING: Journal article

C2 - 29237677

VL - 10

JO - CIRC-CARDIOVASC GENE

JF - CIRC-CARDIOVASC GENE

SN - 1942-325X

IS - 6

ER -