Alpha-adducin Gly460Trp polymorphism, left ventricular mass and plasma renin activity

Objective: Left ventricular hypertrophy (LVH) is associated with an increased risk for cardiovascular morbidity and mortality. Epidemiological studies suggest that LVH may be influenced by genetic factors. However, the evidence associating individual genes with left ventricular (LV) mass is inconsistent and contradictory. Methods: We investigated the association between angiotensin-converting enzyme insertion/deletion, angiotensinogen M235T and α-adducin Gly460Trp polymorphisms with LV mass and plasma renin activity (PRA) in 162 men with mild, never-treated hypertension who were recruited for the Hypertension and Ambulatory Recording Venetia Study. The effect of each polymorphism on LV mass and PRA was tested in one-way analysis of covariance using LV mass index or PRA as the dependent variable after adjusting for covariates. Results: The α-adducin polymorphism was the only individual polymorphism independently associated with LV mass index (F = 7.78, P = 0.006). Patients homozygous for the Trp allele of that polymorphism had a LV mass index (123.4 ± 10.5 g/m²) significantly higher compared with heterozygotes (90.8 ± 2.5 g/m², P < 0.01) or Gly homozygotes (94.7 ± 1.7 g/m², P < 0.05). These subjects also have significantly lower PRA (F = 4.2, P = 0.017). Albeit uncommon, 40% of Trp homozygotes of the α-adducin polymorphism had LVH (odds ratio, 15.1;95% confidence interval, 3.0-82.1). Conclusions: The homozygotic state of the Trp allele of α-adducin Gly460Trp polymorphism is independently associated with increased LV mass and low PRA. These data suggest that genetic considerations may contribute importantly to risk stratification, and perhaps therapeutic interventions targeted at LVH and the renin-angiotensin system in hypertensive patients.