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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
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 confli...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072381/ https://www.ncbi.nlm.nih.gov/pubmed/29237677 http://dx.doi.org/10.1161/CIRCGENETICS.117.001713 |
Sumario: | 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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