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, Jahrgang 10, Nr. 6, 12.2017.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -