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
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Genetics (clinical),Cardiology and Cardiovascular Medicine,Genetics
Cited by
26 articles.
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