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

J Am Coll Cardiol. 2004 Jan 21;43(2):265-70. doi: 10.1016/j.jacc.2003.08.034.

Abstract

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.

Method: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cytochrome P-450 CYP11B2 / genetics*
  • Female
  • Fibrosis / genetics
  • Heart Ventricles / pathology
  • Humans
  • Hypertension / complications
  • Hypertension / genetics*
  • Hypertrophy, Left Ventricular / complications
  • Hypertrophy, Left Ventricular / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*

Substances

  • Cytochrome P-450 CYP11B2