The findings suggested that a common NPPA SNPs rs5063 was associated with serum ANP levels and ANP was prospectively associated with hypertension in the Chinese Han population.
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.
This study examined the SNPs AGT rs699 (Met235Thr), ADD1 rs4961 (rs4961" genes_norm="118">Gly460Trp), NPPArs5063 (Val32Met), GPX1 rs1050450 (Pro198Leu), and AGTR1 rs5186 (A1166C) in relation to hypertension and salt sensitivity.
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.
Variants in the human NPPA gene, encoding the ANP precursor, are associated with hypertension, stroke, coronary artery disease, heart failure (HF) and obesity.
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.
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.
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).
In L-NAME treated rats, relative to Ad.Null or saline administration, Ad.CMV-hAM-4F2 (i) reduced augmented cardiomyocyte membrane protein oxidation and mRNA expression of pro-oxidant (p22phox) and anti-oxidant (SOD-3, GPx) genes; (ii) attenuated increased cardiomyocyte width and mRNA expression of hypertrophic (sk-alpha-actin) and cardio-endocrine (ANP) genes; (iii) did not attenuate hypertension.
Two common single nucleotide polymorphisms (SNPs) in NPPA, rs5063 and rs5065, result in amino acid changes of the primary peptide and have been previously implicated in conditions associated with AF, including stroke 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 conclusion, our findings indicate that the -A2843G polymorphism in the ANP gene promoter might be a genetic risk factor for the development of LVH in patients with hypertension.
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.
The ANP gene, which encodes the precursor of atrial natriuretic peptide (ANP), is among the candidate genes for genetic susceptibility to hypertension.
This suggests that: 1) this I/D dimorphism is not a useful marker to study the relationship between the ANF gene and hypertension in the UAE; and 2) variations of the ANF gene that may be in linkage disequilibrium with this marker do not play a major role in the determination of hypertension in this Arab population.