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

Abstract

The 825T allele of the G-protein b 3 -subunit is associated with increased intracellular signalling. Its association with hypertension is inconsistent. We, therefore, studied the C825T polymorphism in relation to ambulatory blood pressure as well as left ventricular structure and function in two European populations. We genotyped 248 parents and 318 offspring, enrolled in the European Project on Genes in Hypertension in Cracow, Poland (n ¼ 286) and in Novosibirsk, Russian Federation (n ¼ 280). The 24-h ambulatory blood pressure was recorded using oscillometric SpaceLabs 90207 monitors. Within each centre, a single observer performed two-dimensionally guided M-mode echocardiography and Doppler sonography to measure left ventricular structure (American Society of Echocardiography conventions) and diastolic function: early (E) and late (A) peak diastolic inflow velocities. We used analysis of covariance and generalized estimating equations to allow for covariables and nonindependence among related subjects. Genotype frequencies were similar (P ¼ 0.25) in Cracow and Novosibirsk and amounted to 44.7% for CC, 47.2% for CT, and 8.1% for TT. Among parents (mean age: 51.3 years)Fbut not among offspring (mean age 25.1 years)F24-h, daytime and night time systolic blood pressures were 5-6 mmHg higher in TT homozygotes than in C allele carriers. In TT homozygous parents (À8.2 cm/sec, P ¼ 0.004) as well as in TT homozygous offspring (À7.5 cm/sec, P ¼ 0.02), the E-wave was significantly reduced, which in offspring also resulted in a lower E/A ratio (-0.25, P ¼ 0.002). Neither in parents nor in offspring, left ventricular mass index was associated with the C825T polymorphism. In conclusion, in TT homozygotes of both generations, early left ventricular relaxation was reduced. In TT homozygous parents, the latter observation might be because of the higher systolic pressure associated with the TT genotype.

GNB3 gene C825T and ACE gene I/D polymorphisms in essential hypertension in a Kazakh genetic isolate

“…The recent study by Siffert et al 10 reported a positive association between the T variants of the Gb-3-C825T genotype with EH in subjects coming from three areas of Germany. Subsequent report from some researchers in Europe 11,17 and Australia 12 had similar results. However, results of studies investigating the association between the GNB3 C825T polymorphism and hypertension in Japanese, 18 Tanwan Hans, 19 Canadian Oji-cree, 13 and African Americans 14 have proved conflicting.…”

Cognitive Functions across the GNB3C825TPolymorphism in an Elderly Italian Population

“…In our cohort considered as a whole, the cognitive pattern was mildly worse than expected from Italian normative data [35] probably because the TT subjects were more represented in our cohort (15%) than in the European population (8.1–8.4%) [41, 42]. The unfavorable cardiovascular pattern which is typical of the LEOGRA population [20, 21], and which in part derives in turn from the T mutation [2], could also account for impaired cognition.…”

Novel genetic variants contributing to left ventricular hypertrophy: the HyperGEN study

“…Polymorphisms of candidate genes on different chromosomes in diverse pathways (e.g., the angiotensin converting enzyme (ACE) [9], major histocompatibility complex [10], guanine nucleotide-binding protein (GNB3) [11], insulin-like growth factor (IGF-1) [12], and neuropeptide Y (NPY) genes [13]) have been associated with LV mass. However, other studies have failed to replicate the association with some of these polymorphisms (e.g., ACE [14], GNB3 [15]). Evidence of association of other echocardiographic measures of LV geometry with various polymorphisms is nearly equally abundant and similarly contradictory [16, 17].…”