(Hypertension. 1998;32:1094-1097.)
© 1998 American Heart Association, Inc.
Scientific Contributions |
G-Protein ß3 Subunit Gene (GNB3) Variant in Causation of Essential Hypertension
From the Hypertension Gene Laboratory, Department of Physiology and Institute for Biomedical Research, University of Sydney, Sydney, New South Wales (A.V.B., C.L.J., B.J.M.), and Genomics Research Center, School of Health Sciences, Griffith University, Gold Coast, Queensland (D.R.N, L.R.G.), Australia.
Correspondence to Brian J. Morris, DSc, Hypertension Gene Laboratory, Department of Physiology and Institute for Biomedical Research, Building F13, University of Sydney, New South Wales 2006, Australia. E-mail brianm{at}physiol.usyd.edu.au
Abstract—Essential hypertensives
display enhanced signal transduction through pertussis toxin–sensitive
G proteins. The T allele of a C825T variant in exon
10 of the G protein ß3 subunit gene (GNB3) induces
formation of a splice variant (Gß3-s) with enhanced activity. The
T allele of GNB3 was shown recently
to be associated with hypertension in unselected German patients
(frequency=0.31 versus 0.25 in control). To confirm and extend this
finding in a different setting, we performed an association study in
Australian white hypertensives. This involved an extensively
examined cohort of 110 hypertensives, each of whom were the offspring
of 2 hypertensive parents, and 189 normotensives whose parents were
both normotensive beyond age 50 years. Genotyping was performed by
polymerase chain reaction and digestion with BseDI,
which either cut (C allele) or did not cut
(T allele) the 268-bp polymerase chain reaction
product. T allele frequency in the hypertensive
group was 0.43 compared with 0.25 in the normotensive group
(
2=22; P=0.00002; odds ratio=2.3; 95%
CI=1.7 to 3.3). The T allele tracked with higher
pretreatment blood pressure: diastolic=105±7, 109±16, and
128±28 mm Hg (mean±SD) for CC,
CT, and TT, respectively
(P=0.001 by 1-way ANOVA). Blood pressures were higher in
female hypertensives with a T allele
(P=0.006 for systolic and 0.0003 for
diastolic by ANOVA) than they were in male hypertensives.
In conclusion, the present study of a group with strong family
history supports a role for a genetically determined,
physiologically active splice variant of the G
protein ß3 subunit gene in the causation of essential
hypertension.
Key Words: race • hypertension, essential • blood pressure • G protein • genetics
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