The G protein beta3-subunit C825T polymorphism results in a truncated splice variant protein that is associated with enhanced transmembrane signaling, increased proliferative activity, and arterial hypertension. The aim of the present study was to further investigate the association of this polymorphism with left ventricular (LV) structure and function. A total of 2052 individuals from a large-scale population-based sample were investigated for the G protein beta3-subunit C825T polymorphism and echocardiographic parameters of LV structure and function. Complete genotyping and echocardiographic data were available in 1720 individuals (829 men and 891 women). The mean LV mass indices in men with CC (n=384) and TT (n=84) genotypes were 98.3+/-1.2 g/m2 and 100.0+/-2.8 g/m2, respectively (P=0.64). In women, the corresponding values were 83.1+/-1.0 g/m2 for the CC genotype (n=397) and 83.8+/-2.1 g/m2 for the TT genotype (n=91, P=0.32). Likewise, LV dimensions or parameters of the diastolic function and serologic markers of LV mass were not associated with the C825T variant. Finally, multivariate analyses accounting for potentially confounding factors failed to show any influence of this polymorphism on echocardiographic parameters. In conclusion, we were not able to confirm the previously published associations of the G protein beta3-subunit C825T polymorphism with LV structure and diastolic function.