Variants in the human NPPA gene, encoding the ANP precursor, are associated with hypertension, stroke, coronary artery disease, heart failure (HF) and obesity.
If corroborated by other large-scale, prospective studies, our findings indicate that the natriuretic peptide precursor A gene plays a significant role in blood pressure regulation and development of hypertension.
Common genetic variants at the NPPA-NPPB locus found to be associated with circulating natriuretic peptide concentrations contribute to interindividual variation in blood pressure and hypertension.
The natriuretic peptide (NP) family (including ANP (atrial natriuretic peptide), BNP (brain natriuretic peptide), and CNP (C-type natriuretic peptide)), the NP receptors (NPRA, NPRB, and NPRC), and the related protease convertases (furin, corin, and PCSK6) constitute the NP system and represent relevant protective mechanisms toward the development of hypertension and associated conditions, such as atherosclerosis, stroke, myocardial infarction, heart failure, and renal injury.
Clinical trials have documented the benefits and risks of the use of synthetic ANP (Anaritide) and BNP (Nesiritide) for treating heart failure, renal failure, and hypertension.
Common genetic variants at the NPPA-NPPB locus found to be associated with circulating natriuretic peptide concentrations contribute to interindividual variation in blood pressure and hypertension.
In whites, the minor G allele of the atrial natriuretic peptide (ANP) genetic variant rs5068 is associated with higher circulating levels of ANP and B-type natriuretic peptide (BNP), lower risk of hypertension, higher high-density lipoprotein (HDL) cholesterol plasma levels, and lower prevalence of obesity and metabolic syndrome.
Association of atrial natriuretic peptide and type a natriuretic peptide receptor gene polymorphisms with left ventricular mass in human essential hypertension.
Minor alleles of NPPArs5068, rs5065 and rs198358 were associated with less history of hypertension; minor alleles of NPPArs5068 and rs198358 was also associated with higher circulating natriuretic peptide levels (p=0.003 to p=0.04).
Among others, the 2238T>C exon 3 variant has been associated with endothelial cell damage and dysfunction and with an increased risk of acute cardiovascular events, a frameshift mutation within exon 3 has been related to increased risk of atrial fibrillation, and ANP gene variants have been linked to increased risk of hypertension in different ethnic groups.