Association of GNB3 C825T polymorphism with plasma electrolyte balance and susceptibility to hypertension

Abstract

The role of G-protein activation in cardiovascular disorders is well-known. G-protein β3 subunit (GNB3) C825T polymorphism is associated with increased intracellular signal transduction. We investigated the role of the variant in plasma sodium and potassium concentrations and association with hypertension. 345 healthy controls and 455 patients with essential hypertension were enrolled. Plasma renin activity and aldosterone concentration were measured. The variant, typed by SNaPshot, was analyzed on an ABI Prism 3100 Genetic Analyzer and GeneScan. The TT genotype and T allele were over-represented in the patients (p < 0.001, p < 0.0001). Multiple-logistic regression disclosed that the risk of hypertension was significantly greater for TT (p < 0.0001, OR = 6.1, CI = 2.9–12.7). One-way ANOVA revealed that hypertensive T-allele carriers (CT+TT), compared to non-carriers (CC), had a greater body mass index (BMI), mean arterial pressure (MAP) and PAC (p = 0.01, p = 0.01, p < 0.0001, respectively); while the patients with 825TT risk genotype showed higher plasma sodium and lower potassium (p < 0.0001, each). The results strongly emphasize, not only the role of C825T polymorphism by the induction of increased G-protein activity and enhancement of Na/h exchangers, but also the association with higher plasma sodium and lower potassium levels, high BMI and susceptibility to hypertension.

Estimation of the relationship between the polymorphisms of selected genes: ACE, AGTR1, TGFβ1 and GNB3 with the occurrence of primary vesicoureteral reflux

“…Hyperfiltration can be caused by disorders of renal autoregulation causing as a consequence, transferring of high system pressure on the renal glomerulus [ 100 , 101 ]. Numerous studies indicate the pathogenic importance of carriers of the mutated T allele polymorphism rs5443 in terms of susceptibility to hypertension, having the character of low-renin hypertension [ 81 , 102 ]. Among the hypothetical mechanisms of its development is taken into account inter alia increased activity of sodium-hydrogen exchanger NHE-1, the function of which 30–50% is mediated by G proteins and increased reactivity of vascular smooth muscle to vasoconstrictive factors, such as acting through G protein, norepinephrine and angiotensin II [ 81 , 103 ].…”

“…Numerous studies indicate the pathogenic importance of carriers of the mutated T allele polymorphism rs5443 in terms of susceptibility to hypertension, having the character of low-renin hypertension [ 81 , 102 ]. Among the hypothetical mechanisms of its development is taken into account inter alia increased activity of sodium-hydrogen exchanger NHE-1, the function of which 30–50% is mediated by G proteins and increased reactivity of vascular smooth muscle to vasoconstrictive factors, such as acting through G protein, norepinephrine and angiotensin II [ 81 , 103 ]. Observation of patients after kidney transplantation has brought an interesting suggestion that the higher blood pressure seen in those with the TT genotype polymorphism C825T may be responsible for the deterioration of renal function [ 104 ].…”

Interactions between the FTO and GNB3 Genes Contribute to Varied Clinical Phenotypes in Hypertension

“…Literature suggested an association of the FTO variants with hypertension [18], [23] or mediation through other hypertension risk factors like BMI or adiposity [10], [12], [31], [32]. Likewise, given the role of heterotrimeric G-proteins in intracellular signaling pathways, the GNB3 variants were studied in EH [20]–[22], [33]. The rs5443C/T of GNB3 was associated with enhanced activation of G protein-mediated signaling [20], noradrenaline-induced vasoconstriction [34], higher plasma sodium and lower potassium levels [33] and the C allele of rs1129649T/C was associated with salt sensitive BP [35].…”

Association of C825T polymorphism β3-subunit G-protein with hypertension

“…У контрольованих популяційних дослідженнях, проведених серед європейців [12] та жителів Індії [5], продемонстровано зв'язок Т алеля з розвитком АГ. Встановлено більш високу частоту Т алеля (0,526) у хворих на АГ, а також асоціацію даного поліморфізму з початком АГ у більш ранньому віці і з більш злоякісним перебігом [7].…”