G-Protein β ₃ -Subunit Gene 825T Allele and Hypertension

Abstract

Abstract-The 825T allele of the GNB3 gene has been associated with essential hypertension and obesity in cross-sectional studies. We have therefore planned a longitudinal cohort study to assess whether the GNB3 825T allele is predictive of blood pressure increase in young subjects with grade I hypertension. We genotyped at the GNB3 oth genetic and environmental factors contribute to the pathogenesis of essential hypertension. Hypertension is about twice as common in subjects who have one or two hypertensive parents, and many epidemiological studies suggest that genetic factors account for approximately 30% of the variation in blood pressure in various populations. 1 Polymorphisms in several genes has been associated with blood pressure levels. 2 Siffert et al 3 described a C825T polymorphism in the GNB3 gene encoding the ␤ 3 -subunit of heterotrimeric G proteins, with the 825T allele being associated with alternative splicing of the gene, hypertension, and increased body mass index (BMI). 4,5 The 825T allele has been shown to be associated also with diastolic dysfunction, 6 increased left ventricular mass index, 7 and increased risk for left ventricular hypertrophy in patients with hypertension. 8 However, the association of T allele with hypertension and other cardiovascular risk factors has been disputed in recent studies. 9 -11 A large cross-sectional study could not show association between GNB3 genotypes and left ventricular hypertrophy. 9 Hengstenberg and coworkers 12 confirmed the association between the 825T allele and hypertension, whereas Snapir et al 11 produced negative results. However, in that latter study, the number of 825T allele carriers was remarkably low.All the previous studies selected patients from a largescale, population-based sample, pooling together normotensive subjects, hypertensive patients, and patients taking antihypertensive medications. Moreover, all but one study 11 were cross-sectional and included patients with a broad range of age and cardiovascular risks.The GNB3 polymorphism has never been formally tested as a potential marker of risk for development of hypertension, and up to now it is unclear to what extent the 825T allele has a direct effect on blood pressure, independent of body weight and other potential confounders such as age and drug treatment. Therefore, to avoid the effect of these confounders on blood pressure, we studied a homogeneous cohort of young, never-treated patients with stage I hypertension. The aim of our study was to investigate in these subjects whether the 825T allele was associated with increased risk of development of more severe hypertension during long-term follow-up.

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

“…Hypertension is the phenotype of the metabolic syndrome that has been most frequently studied in relation to the GNB3 825C>T polymorphism [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]17]. In this study we did not show a relationship between the polymorphism and hypertension defined according to the WHO 1999 criteria.…”

“…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].…”

Office Pulse Pressure Is a Predictor of Favorable Outcome in Young- to Middle-Aged Subjects With Stage 1 Hypertension

“…[11][12][13] Only subjects who had at least 6 months of follow-up were included. Patients' recruitment was obtained with the collaboration of the local general practitioners who were instructed during local meetings.…”

“…Baseline data included a medical and family history and a selfcompiled questionnaire about lifestyle habits: current use of coffee and alcoholic beverages, smoking status, and physical activity habits. [11][12][13] Other details are reported in the online-only Data Supplement. Brachial office BP at entry was the mean of 6 measurements obtained with a mercury sphygmomanometer with appropriately sized cuffs, during 2 visits performed 2 weeks apart.…”

Geneticism of Essential Hypertension

“…Recently, a longitudinal study of 461 persons observed over the course of 5 years suggested that individuals with the 825T allele progressed to hypertension more rapidly than those who did not. 11 Perhaps the only happy note is that an increased response to sildenafil occurs in those carrying the 825T allele.…”