Association of atrial natriuretic peptide and type a natriuretic peptide receptor gene polymorphisms with left ventricular mass in human essential hypertension.
OBJECTIVE
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.
Rubattu
Speranza
S
IRCCS Neuromed, Polo Molisano University of Rome La Sapienza, Pozzilli, Italy. rubattu.speranza@neuromed.it
Bigatti
Giada
G
Evangelista
Anna
A
Lanzani
Chiara
C
Stanzione
Rosita
R
Zagato
Laura
L
Manunta
Paolo
P
Marchitti
Simona
S
Venturelli
Vanessa
V
Bianchi
Giuseppe
G
Volpe
Massimo
M
Stella
Paola
P
D000225:Adenine; D000328:Adult; D000483:Alleles; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000235:genetics*; D003596:Cytosine; D004452:Echocardiography; D005260:Female; D014644:Genetic Variation; D006147:Guanine; D006162:Guanylate Cyclase / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000235:genetics*; D007438:Introns; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics*; D013941:Thymine; D020257:Ventricular Remodeling / Q000235:genetics
D020097:Natriuretic Peptide, Brain; D006147:Guanine; D009320:Atrial Natriuretic Factor; D003596:Cytosine; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; D000225:Adenine; D013941:Thymine