Relation of the G Protein β ₃ -Subunit Polymorphism With Left Ventricle Structure and Function

Abstract

Abstract-The G protein ␤ 3 -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 ␤ 3 -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 (nϭ384) and TT (nϭ84) genotypes were 98.3Ϯ1.2 g/m 2 and 100.0Ϯ2.8 g/m 2 , respectively (Pϭ0.64). In women, the corresponding values were 83.1Ϯ1.0 g/m 2 for the CC genotype (nϭ397) and 83.8Ϯ2.1 g/m 2 for the TT genotype (nϭ91, Pϭ0.32). 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 ␤ 3 -subunit C825T polymorphism with LV structure and diastolic function.

The GNB3 C825T polymorphism and essential hypertension: a meta-analysis of 34 studies including 14 094 cases and 17 760 controls

“…These studies were used only once and participated in the sensitivity analysis. One initially identified study [29] was excluded, since it comprised the same subjects as a study already included [23]. The detailed characteristics of each study (country conducted, racial descent of subjects involved, characteristics of cases and controls, sample size, etc.)…”

Ambulatory blood pressure and left ventricular structure and function in relation to the G-protein β3-subunit polymorphism C825T in White Europeans

“…26,27 In contrast, a large population-based study did not reveal any association between cardiac structure and GNB3 T allele. 28 Association never proves causation. Nevertheless, several mechanisms may explain why early left ventricular relaxation may be impaired in the presence of the 825T allele.…”

Studies of the association of the GNB3 825C>T polymorphism with components of the metabolic syndrome in white Danes

“…Due to their pivotal function in many cell types, variation in the genes encoding the subunits of G proteins has the potential to play a role in numerous clinical conditions. Specifically, investigators have studied possible associations of the frequent substitution of a C with a T nucleotide at position 825 in exon 10 in the gene encoding the G protein β3 subunit (GNB3), resulting in the silent Ser275Ser polymorphism, with hypertension [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] and related cardiovascular phenotypes [16][17][18][19][20][21][22], and with obesity [22][23][24][25], psychological syndromes [26][27][28], type 1 diabetes complications (nephropathy, retinopathy and neuropathy) [29,30], type 2 diabetes [13,22,31,32], cancer [33] and various immunological responses [34]. The 825C>T polymorphism is associated with the occurrence of a splice variant with an in-frame deletion of 41 amino acids (from exon 9) including the fourth of seven Trp-Asp repeats, each consisting of approximately 40 highly conserved amino acids, which normally form a β-propeller peptide structure [1].…”