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CLINICAL RESEARCH: HYPERTENSION

Association of Atrial Natriuretic Peptide and Type A Natriuretic Peptide Receptor Gene Polymorphisms With Left Ventricular Mass in Human Essential Hypertension

Speranza Rubattu, MD^_*,,_*, Giada Bigatti, MD, Anna Evangelista, PhD^_*, Chiara Lanzani, MD, Rosita Stanzione, PhD^_*, Laura Zagato, BBSC, Paolo Manunta, MD, Simona Marchitti, BS^_*, Vanessa Venturelli, MD, Giuseppe Bianchi, MD, Massimo Volpe, MD^_*, and Paola Stella, MD

^_* IRCCS Neuromed, Polo Molisano University of Rome La Sapienza, Pozzilli, Italy
U.O. Cardiologia, II^nd School of Medicine, University of Rome La Sapienza, S. Andrea Hospital, Rome, Italy
Division of Nephrology, Dialysis and Hypertension, University Vita e Salute, San Raffaele Hospital, Milan, Italy.

Manuscript received July 23, 2005; revised manuscript received December 7, 2005, accepted December 13, 2005.

^_* Reprint requests and correspondence: Dr. Speranza Rubattu, IRCCS Neuromed, Localit Camerelle, 86077 Pozzilli (Isernia), Italy. (Email: rubattu.speranza{at}neuromed.it).

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.

Abbreviations and Acronyms   ANOVA = analysis of variance   ANP = atrial natriuretic peptide   BNP = brain natriuretic peptide   BP = blood pressure   LVH = left ventricular hypertrophy   LVM = left ventricular mass   NPRA = type A natriuretic peptide receptor   RFLP = restriction fragment length polymorphism   ST = septal thickness

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