Enhanced epinephrine‐induced platelet aggregation in individuals carrying the G protein β3 subunit 825T allele

Naber, Christoph; Hermann, Burkhard Lorenz; Vietzke, Delia; Altmann, Christoph; Haude, Michael; Mann, Klaus; Rosskopf, Dieter; Siffert, Winfried

doi:10.1016/s0014-5793(00)02158-x

Cited by 36 publications

(16 citation statements)

References 21 publications

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“…3 Furthermore, G-protein activation is increased to a similar extent, 3 and the associated cellular phenotypes, like chemotaxis, 22 agonist-induced vasoconstriction, 23,24 and epinephrineinduced platelet aggregation, 25 are virtually identical in cells with TC or TT genotype but increased in comparison with those with CC genotype. For these reasons and because the TT genotype is relatively rare in white populations, in previous studies patients homozygous or heterozygous (TT and TC genotypes, respectively) were combined for analysis.…”

Section: Resultsmentioning

confidence: 91%

“…22 In platelets, aggregation after epinephrine and after the combination of epinephrine and ADP was significantly enhanced in carriers of the 825T allele. 25 Increased G-protein activation is not only observed in vitro 3 but also in cells studied ex vivo. 22,25 Baumgart et al 23 have shown in vivo an increased constriction of coronary arteries after a bolus intravenous injection of an ␣ 2 -adrenoceptor-activating compound in 825T allele carriers.…”

Section: Discussionmentioning

confidence: 99%

“…25 Increased G-protein activation is not only observed in vitro 3 but also in cells studied ex vivo. 22,25 Baumgart et al 23 have shown in vivo an increased constriction of coronary arteries after a bolus intravenous injection of an ␣ 2 -adrenoceptor-activating compound in 825T allele carriers. Furthermore, vasoconstriction in response to endothelin-1, angiotensin II, and noradrenaline was significantly enhanced in the skin microcirculation in healthy carriers of the 825T allele.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2003

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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.

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Section: Resultsmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2003

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“…There are, however, alternative ways the C825T polymorphism could influence incidence of or mortality in MI: Dobrev et al [24] have shown altered cardiac potassium currents in homozygous carriers of the T allele, an observation that gives reason to speculate whether carriers of the 825T allele might be more prone to malignant arrythmia, a commonly lethal complication in myocardial infarctions. Also the recently observed enhanced epinephrine-induced platelet aggregation in individuals with the 825T allele [25] could very well be a contributing factor to the death from MI. Finally an increased vasoconstriction was recently observed [26] in carriers of the T-allele.…”

Section: Discussionmentioning

confidence: 97%

DNA polymorphisms in the tyrosin hydroxylase and GNB3 genes: association with unexpected death from acute myocardial infarction and increased heart weight

Klintschar

Stiller

Schwaiger

et al. 2005

Forensic Science International

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“…1 In this context it is of importance, that genetic variants were also shown to alter aggregation, as in platelets obtained from carriers of the G␤3 825T allele, the slopes and maximum of secondary aggregation were significantly enhanced after epinephrine challenge. 37 This phenomenon appeared independent of platelet secretion or inhibition of the adenylylcyclase and may suggest that this enhanced reactivity might also increase platelet reactivity in vivo.…”

Section: Combined Analysismentioning

confidence: 91%

Combined action of the ACE D- and the G-protein β3 T-allele in major depression: a possible link to cardiovascular disease?

Bondy¹,

Baghai²,

Zill³

et al. 2002

Mol Psychiatry

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Although it is well established that depression is a major risk factor for the development of coronary artery disease and that cerebrovascular disease can be a major contributing factor for the development of depression, the information about the interplay between the central nervous system and cardiovascular disease is still limited. We investigated the angiotensin I converting enzyme (ACE) ID and the G-protein ␤3-subunit (G␤3) C825T polymorphism in 201 patients with unipolar major depression and 161 ethnically and age-matched controls. Both gene variants have earlier been associated with either cardiovascular disease or affective disorders, making them good candidates for a combined analysis. We found a significant increase in the G␤3 T allele (OR = 1.61, 95% CI 1.17-2.2, P = 0.0035) and a marginal altered genotype distribution of the ACE ID polymorphism with decrease in the II genotypes ( 2 = 6.43, df=3, P = 0.04) in the patients' group. Analysing the data for both genes we found that the combined actions of ACE and G␤3 genotypes accumulate in carriers of the ACE D allele (ID and DD) and G␤3 TT homozygotes with ID/DD-TT carriers showing a more than five-fold increase in risk for major depression (crude OR = 5.83, 95% CI 1.99-17.08, P = 0.0002). As our study was carried out with depressive patients without serious cardiac impairment at the time of the investigation, we are presently unable to predict whether this combined action of the ACE ID/DD-G␤3 TT genotype is increasing the risk for both disorders. Nevertheless our study reports for the first time that the same allelic combination of two genes that have been shown to increase the risk for myocardial infarction (Naber et al, 2000) increase the vulnerability for depressive disorder.

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Enhanced epinephrine‐induced platelet aggregation in individuals carrying the G protein β3 subunit 825T allele

Cited by 36 publications

References 21 publications

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

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

DNA polymorphisms in the tyrosin hydroxylase and GNB3 genes: association with unexpected death from acute myocardial infarction and increased heart weight

Combined action of the ACE D- and the G-protein β3 T-allele in major depression: a possible link to cardiovascular disease?

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Enhanced epinephrine‐induced platelet aggregation in individuals carrying the G protein β3 subunit 825T allele

Cited by 36 publications

References 21 publications

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

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

DNA polymorphisms in the tyrosin hydroxylase and GNB3 genes: association with unexpected death from acute myocardial infarction and increased heart weight

Combined action of the ACE D- and the G-protein β3 T-allele in major depression: a possible link to cardiovascular disease?

Contact Info

Product

Resources

About

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

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