Association of atrial natriuretic peptide and type A natriuretic peptide receptor gene polymorphisms with left ventricular mass in human essential hypertension

OBJECTIVES The goal of our study was to investigate the relationships between atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and type A natriuretic peptide receptor (NPRA) gene polymorphisms and left ventricular structure in human essential hypertension. BACKGROUND Experimental evidence supports a key role for natriuretic peptides in the modulation of cardiac mass. This relationship has not yet been described in human disease. METHODS A total of 203 hypertensive patients were studied by mono-bidimensional echocardiography. Three markers of the ANP gene (-C664G, G1837A, and T2238C polymorphisms) and a microsatellite marker of both NPRA and BNP genes were characterized. RESULTS Patients carrying the ANP gene promoter allelic variant had increased left ventricular mass index (117.4 +/- 1.7 g vs. 95.7 +/- 1.7 g, p = 0.005), left ventricular posterior wall thickness (1.14 +/- 0.07 cm vs. 0.96 +/- 0.01 cm, p < 0.0001), left ventricular septal thickness (1.12 +/- 0.10 cm vs. 1.04 +/- 0.01 cm, p = 0.01), and relative wall thickening (47.5 +/- 4.1% vs. 39.4 +/- 5.3%, p = 0.001) as compared with the wild-type genotype. These associations were independent from anthropometric factors and major clinical features and were confirmed in a large subgroup of never-treated hypertensive patients (n = 148). Carrier status of the ANP gene promoter allelic variant was associated with significantly lower plasma proANP levels: 1,395 +/- 104 fmol/ml versus 3,110 +/- 141 fmol/ml in hypertensive patients carrying the wild-type genotype (p < 0.05). A significant association for NPRA gene variants with left ventricular mass index and left ventricular septal thickness was found. The analysis of BNP did not reveal any effect on cardiac phenotypes. CONCLUSIONS Our findings show that the ANP/NPRA system significantly contributes to ventricular remodeling in human essential hypertension.