The Arg16Gly Polymorphism of the β2-Adrenergic Receptor and Left Ventricular Systolic Function

Background: β-Adrenergic receptors (ARs), including β1- and β2-AR, are involved in modulation of cardiac contractility and heart rate. Arg16Gly, a functional polymorphism in the β2-AR gene, has been reported to influence exercise capacity in heart failure patients. This study examined the association of the β2-AR Arg16Gly polymorphism with left ventricular (LV) systolic function in a biethnic population-based sample. Methods: Echocardiograms and the β2-AR Arg16Gly polymorphism were analyzed in 267 normotensive (54% African Americans) and 252 severe hypertensive (53% African Americans) adults without coronary heart disease or diabetes. Results: The frequencies of Gly16Gly16, Arg16Gly16, and Arg16Arg16 were 28.1%, 54.3%, and 17.6%, respectively, in normotensives, and 31.4%, 47.6%, and 21.0%, respectively, in hypertensives. In normotensives, the Gly16Gly16 homozygotes displayed greater fractional shortening (35.9% ± 4.3% v 34.1% ± 4.7% v 34.0% ± 3.9%, P = .01), ejection fraction (65.0% ± 5.8% v 62.5% ± 6.4% v 62.6% ± 5.4%, P = .01), midwall shortening (18.6% ± 1.6% v 17.9% ± 1.9% v 18.0% ± 1.6%, P = .02), and stress-corrected midwall shortening (110.1% ± 9.3% v 106.1% ± 10.6% v 108.1% ± 10.8%, P = .03) compared to the Arg16Gly16 and Arg16Arg16 groups. These associations were independent of age, sex, ethnicity, heart rate, body mass index, systolic blood pressure, LV end-diastolic dimension, and field center. No significant associations between the β2-AR Arg16Gly polymorphism and echocardiographic measures were found in hypertensives. Conclusions: The Arg16Gly polymorphism of β2-AR may be a marker for LV chamber function and contractility in normotensive adults.