Adducin 1 (alpha) Gly460Trp Variant is Associated with Left Ventricular Geometry in Caucasians and African Americans: The HyperGEN Study

Normal left ventricular (LV) mass and geometry is required for optimal LV functioning. Abnormalities in either result in increased morbidity and mortality. The adducing 1 (alpha) gene (ADD1) Gly460Trp polymorphism has been associated with high blood pressure and increased plasma volume, both predictors of LV mass and function. In this cross-sectional study, we evaluate the association between this polymorphism and LV mass and geometry. LV mass, relative wall thickness (RWT), and systolic and diastolic parameters were measured using echocardiography in 3483 African American and Caucasian subjects from the Hypertension Genetic Epidemiology Network (HyperGEN). Analysis of covariance was used to estimate the polymorphism's association with echocardiograph parameters, stratified by race. The model was adjusted for age, diastolic and systolic blood pressure, glomerular filtration rate, smoking, low and high density lipoprotein cholesterol, urinary sodium, and body mass index. In Caucasians, the Trp allele was associated with higher ejection fraction (EF) (P = .02), fractional shortening (FS) (P = .02), and RWT (P = .03). In African Americans, the Trp allele was negatively associated with RWT (P = .02), but no association was found with EF (P= .08) or FS (P= .09). The polymorphism was not associated with diastolic function parameters in either racial group. We found no association of ADD1 Gly460Trp with LV mass in Caucasians or African Americans; however, it was associated with unfavorable LV geometry (higher RWT) in Caucasians and favorable LV geometry (lower RWT) in African Americans after controlling for factors that would affect plasma volume.