Effect of the C825T polymorphism of the G protein beta 3 subunit on the systolic blood pressure-lowering effect of clonidine in young, healthy male subjects.
The T allele of the C825T polymorphism in the gene encoding the G-protein beta 3 subunit (GNB3) is associated with hypertension. An enhanced signal transduction in response to alpha(2)-adrenergic receptor stimulation has been shown in carriers of the T allele in vitro. We hypothesized that T allele carriers would show an enhanced antihypertensive response to stimulation of central alpha(2)-adrenergic receptors by clonidine. We compared the response to intravenous clonidine in 30 young, healthy male subjects with and without the T allele (15 CC, 10 CT, and 5 TT). Clonidine lowered blood pressure and total peripheral resistance, lengthened the duration of electromechanical systole (QS(2)c), and slowed down pulse wave velocity. Carriers of the T allele showed significantly greater reductions in systolic blood pressure (P =.009; mean change +/- SEM: CC, -8.9 +/- 0.5; CT and TT, -10.6 +/- 0.4) and total peripheral resistance (P <.0001; mean change +/- SEM: CC, 40 +/- 17; CT and TT, -48 +/- 14) and more marked lengthening of QS(2)c (P =.002; mean change +/- SEM: CC, 2.2 +/- 0.5; CT and TT, 4.7 +/- 0.6) and slowing of pulse wave velocity (P =.012; mean change +/- SEM: CC, -0.25 +/- 0.02; CT and TT, -0.33 +/- 0.03). The results of this study suggest that the 825T allele may be a relevant pharmacogenetic marker in the use of centrally acting sympatholytic drugs.
Nürnberger
Jens
J
Department of Medicine, Essen University, Germany.
Dammer
Sandra
S
Mitchell
Anna
A
Siffert
Winfried
W
Wenzel
René R
RR
Gössl
Mario
M
Philipp
Thomas
T
Michel
Martin C
MC
Schäfers
Rafael F
RF
D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics*; D003000:Clonidine / Q000494:pharmacology*; D003596:Cytosine; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000502:physiology*; D021122:Protein Subunits / Q000235:genetics*; D013941:Thymine
C454420:G-protein beta3 subunit; D021122:Protein Subunits; D003596:Cytosine; D020962:Heterotrimeric GTP-Binding Proteins; D003000:Clonidine; D013941:Thymine