From the Klinik und Poliklinik für Innere Medizin II,
Universität Regensburg, Regensburg (H.S., G.A.J.R.); Institut für
Epidemiologie und Sozialmedizin, Universität Münster, Münster
(H.-W.H.); and GSF Forschungszentrum, Institut für Epidemiologie,
München-Neuherberg (H.-W.H.); and Institut für Pharmakologie,
Universitätsklinikum Essen, Essen (W.S.), Germany.
Correspondence to Dr H. Schunkert, Klinik und Poliklinik für Innere Medizin II, University of Regensburg, D-93042 Regensburg, Germany. E-mail heribert.schunkert{at}klinik.uni-regensburg.de
Abstract—Gi proteins
mediate the intracellular effects of many vasoactive and proliferative
stimuli. Recently such signaling was found to be enhanced in cultured
cells of some hypertensive subjects. A polymorphism at position 825
(C
© 1998 American Heart Association, Inc.
Scientific Contributions
Association Between a Polymorphism in the G Protein ß3 Subunit Gene and Lower Renin and Elevated Diastolic Blood Pressure Levels
T) of the G protein ß3 subunit gene (GNB3) was strictly related
to this phenotype. The aim of the present investigation was
to test the association between this polymorphism and blood
pressure and plasma renin levels in humans. A population-based sample
(n=608) was analyzed by questionnaire and characterized for
blood pressure; plasma renin, prorenin, and aldosterone
levels; and Gß3 C825T allele status. In individuals
without antihypertensive medication (n=474; age range, 52 to 67 years),
the polymorphism was mildly associated with diastolic
blood pressure (CC: 88.6±0.3 mm Hg, n=218; versus CT:
90.1±0.7 mm Hg, n=209; versus TT: 91.8±1.7 mm Hg, n=47;
P=0.02 for trend) but not with systolic blood
pressure. Furthermore, the 825T allele was also significantly
associated with lower renin and prorenin levels, whereas the
aldosterone to renin ratio was elevated in these subjects.
Significant associations between the 825T allele and
diastolic blood pressure, plasma renin, and prorenin levels
(inverse), and the aldosterone to renin ratio persisted
after adjustment for age, gender, body mass index, and systolic
blood pressure. Finally, when the entire sample was considered and an
adjustment was made for covariates, the presence of
arterial hypertension and the use of antihypertensive
medication were both 1.8-fold higher in the TT than in the CC
genotype group (P<0.05 and
P=0.06, respectively). This observation, if replicated
in further studies, suggests a molecular mechanism that unifies a
higher diastolic blood pressure, a lower renin level, and
an elevated aldosterone to renin ratio, ie, a combination
of features frequently found in patients with arterial
hypertension.
Key Words: hypertension • G protein • genetics • genotype • medication • renin
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