825T allele of the G-protein β₃ subunit gene (GNB3) is associated with impaired left ventricular diastolic filling in essential hypertension

Objective. Recently, a novel C825T polymorphism in the gene (GNB3) encoding for the G-protein β₃ subunit was identified. The 825T allele is associated with the generation of a novel splice variant, enhanced intracellular signal transduction, and arterial hypertension. In this study, we investigated the impact of the 825T allele on left ventricular structure and function in mild to moderate essential hypertensive subjects. Methods. In 34 white patients with established mild to moderate essential hypertension (World Health Organization stage I or II, mean age 52 ± 9 years) genotype analysis of GNB3 C825T polymorphism, insertion/deletion polymorphism of the ACE gene and 1166 A/C polymorphism of the AT₁ receptor gene was performed. In each patient, 24 h ambulatory blood pressure measurement (SpaceLabs 90207) and two-dimensional guided M-mode echocardiography combined with Doppler sonography were performed. Results. In our homogenous study group, the GNB3 825T allele was not associated with casual and 24 h ambulatory blood pressure (CC versus TC/TT: 144 ± 13/92 ± 8 versus 151 ± 14/97 ± 7 and 143 ± 11/92 ± 7 versus 150 ± 16/96 ± 9 mmHg, respectively) or parameters of left ventricular structure (relative wall thickness: CC versus TC/TT, 0.48 ± 0.1 versus 0.46 ± 0.1; left ventricular mass: CC versus TC/TT, 281 ± 65 versus 299 ± 80 g). However, transmitral flow variables reflecting left ventricular diastolic filling were impaired in patients expressing the TC/TT genotype (ratio of peak late (A) to early (E) velocities: CC versus TC/TT, 0.95 ± 0.24 versus 1.2 ± 0.26, P < 0.02; velocity time integrals A/E: CC versus TC/TT, 0.57 ± 0.16 versus 0.76 ± 0.23, P < 0.01) while all co-variables such as age, body mass index, ambulatory blood pressure, heart rate and end-diastolic volume were similar between the two groups. If patients were stratified according to the I/D polymorphism of the ACE gene and the A1166C polymorphism of the AT₁ receptor gene, no differences in blood pressure, left ventricular structure or systolic and diastolic function of the left ventricle were found between different genotypes. Conclusion. The GNB3 825T allele was associated with impaired left ventricular diastolic filling in hypertensive subjects in this study. Since alterations in left ventricular filling have been identified as an early marker of hypertensive heart disease, the GNB3 C825T polymorphism may influence cardiac adaptation to increased afterload.