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Effect of the C825T Polymorphism of the G Protein β3 Subunit on the Systolic Blood Pressure–Lowering Effect of Clonidine in Young, Healthy Male Subjects
Author(s) -
Nürnberger Jens,
Dammer Sandra,
Mitchell Anna,
Siffert Winfried,
Wenzel René R.,
Gössl Mario,
Philipp Thomas,
Michel Martin C.,
Schäfers Rafael F.
Publication year - 2003
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(03)00087-0
Subject(s) - clonidine , medicine , endocrinology , allele , blood pressure , stimulation , allele frequency , biology , gene , genetics
The T allele of the C825T polymorphism in the gene encoding the G‐protein β3 subunit ( GNB3 ) is associated with hypertension. An enhanced signal transduction in response to α 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 α 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. Clinical Pharmacology & Therapeutics (2003) 74 , 53–60; doi: 10.1016/S0009‐9236(03)00087‐0