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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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 ' , Circulation. Cardiovascular genetics , vol. 10 , no. 6 , 001713 . https://doi.org/10.1161/CIRCGENETICS.117.001713

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
Author: 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
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Clinicum
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2017-12
Number of pages: 9
Belongs to series: Circulation. Cardiovascular genetics
ISSN: 1942-325X
URI: http://hdl.handle.net/10138/230825
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=27059). 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=8.2x10(-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.
Subject: blood pressure
genes
genome-wide association study
hypertension
natriuretic peptide
brain
HEART-FAILURE
TRANSGENIC MICE
RISK
HYPERTENSION
FINLAND
DISEASE
CLONING
MODEL
DNA
3111 Biomedicine
3121 Internal medicine
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