Key result
Genetic variants increasing MR-proANP concentration were associated with a 9% decrease in the odds of hypertension per unit increase in allele score, whereas BNP-associated variants had no effect on blood pressure.
Why the study?
Do genetic variants affecting ANP and BNP concentrations influence blood pressure in the general population?
Observational (n=33,355)
Yes
Do genetic variants affecting ANP and BNP concentrations influence blood pressure in the general population?
Genetically determined increases in ANP, but not BNP, are associated with lower blood pressure, highlighting ANP as a key regulator of blood pressure in the general population.
Answers are grounded in this paper and cite their sources.
Supports ANP but not BNP in BP regulation; leaves open causal effects and therapeutic implications.
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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Salo et al. (2017) conducted an observational in General population (blood pressure regulation) (n=33,355). Genetic variants affecting ANP and BNP concentrations vs. Reference alleles was evaluated on Hypertension risk (OR 0.91, p=8.2x10^-4). Genetic variants increasing MR-proANP concentration were associated with a 9% decrease in the odds of hypertension per unit increase in allele score, whereas BNP-associated variants had no effect on blood pressure.
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