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CLINICAL RESEARCH: HYPERTENSION

Association between aldosterone synthase (CYP11B2) polymorphism and left ventricular mass in human essential hypertension

Paola Stella, MD^*,*, Giada Bigatti, MD, Laura Tizzoni, BBSC^*, Cristina Barlassina, BBSC, Chiara Lanzani, MD^*, Giuseppe Bianchi, MD^* and Daniele Cusi, MD

^* Division of Nephrology, Dialysis and Hypertension, Graduate School of Nephrology, University "Vita e Salute" San Raffaele, MilanItaly
Graduate School of Nephrology, University of Milan, Milan, Italy

^* Reprint requests and correspondence: Dr. Paola Stella, Division of Nephrology, Dialysis and Hypertension, University "Vita e Salute" San Raffaele, Via Olgettina 60, 20132 Milan, Italy.
paola.stella{at}hsr.it

OBJECTIVES: The aim of our study was to evaluate the relationship between aldosterone synthase gene polymorphism and cardiac dimensions in essential hypertension.

BACKGROUND: Higher aldosterone synthase messenger ribonucleic acid levels in the human heart are accompanied by increased intracardiac aldosterone production, a phenomenon that is associated with cardiac fibrosis and hypertrophy. Recent evidence suggests that a polymorphism (–344C/T) in the promoter region of the aldosterone synthase gene is associated with increased constitutive aldosterone production.

METHODS: Relationships between M-mode echocardiographic cardiac dimensions and aldosterone synthase –344C/T polymorphism were studied in 210 never-treated, middle-aged patients (age 41.6 ± 1.4 years) affected by mild to moderate essential hypertension. Among these patients, 48 had the genotype –C344C, 97 had –C344T, and 65 had –T344T. Patients in the three groups were similar in terms of age, gender, body mass index, and blood pressure.

RESULTS: Left ventricular (LV) mass and thickness were positively correlated with the number of T alleles: LV mass (CC, CT, and TT, respectively: 168 ± 6.9, 179 ± 5.2, and 193 ± 6.9 g; p = 0.03), LV septal thickness (0.99 ± 0.02, 1.03 ± 0.02, and 11.08 ± 0.03 cm, p = 0.04), PWT (0.93 ± 0.03, 0.95 ± 0.01, and 1.03 ± 0.02 cm; p = 0.002), and relative wall thickness (38.3 ± 1.2%, 38.8 ± 0.8%, and 42.8 ± 1.1%; p = 0.004). This trend was confirmed by linear regression, suggesting a "major gene" behavior for the T allele. Multiple regression analysis showed that this effect was independent of anthropometric and clinical factors, including adrenal aldosterone.

CONCLUSIONS: Our data suggest that –344C/T polymorphism affects LV mass and thickness in essential hypertension, independent of adrenal aldosterone. A role for intracardiac aldosterone synthesis is hypothesized.

Abbreviations and Acronyms   BP = blood pressure   LV = left ventricle/ventricular   LVH = left ventricular hypertrophy   LVM = left ventricular mass   PRA = plasma renin activity   PWT = posterior wall thickness   RWT = relative wall thickness   ST = septal thickness

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