From Robarts Research Institute and Department of Medicine (R.A.H., H.C.)
and Thames Valley Family Practice Research Unit (S.B.H.), University of
Western Ontario, London, Ontario, Canada; and Samuel Lunenfeld Research
Institute, Mount Sinai Hospital, and Department of Medicine, University of
Toronto, Toronto, Ontario, Canada (A.J.G.H., B.Z.).
Correspondence to Robert A. Hegele, MD, Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, 406-100 Perth Dr, London, Ontario, Canada N6A 5K8. E-mail robert.hegele{at}rri.on.ca
Abstract—The subunits of the
heterotrimeric G proteins are attractive candidate gene products
for both susceptibility to essential hypertension and interindividual
variation in blood pressure. There is alternative splicing of exon 9 of
the gene encoding the ß3 subunit of heterotrimeric G proteins
(GNB3) associated with a C
© 1998 American Heart Association, Inc.
Scientific Contributions
G Protein ß3 Subunit Gene Variant and Blood Pressure Variation in Canadian Oji-Cree
T change at
nucleotide 825, which activates a cryptic splice
site. The 825T allele results in a gene product that is 41
amino acids smaller than the wild-type gene product. G protein
heterotrimers containing the shorter variant are more reactive than
those containing the wild type, and the 825T allele appears to be
associated with essential hypertension. To evaluate whether this
variant is associated with hypertension or blood pressure in other
human samples, we genotyped 447 young adult Oji-Cree for the
GNB3 C825T variation. We found that the frequency of the
GNB3 825T allele was 0.501 in the Oji-Cree, which is
considerably higher than the frequency observed in whites. Furthermore,
genetic variation of the GNB3 nucleotide 825
was significantly associated with variation in systolic
pressure but not diastolic pressure. Specifically, subjects
with the 825T/T genotype had significantly lower
systolic pressure than subjects with the 825C/T and 825C/C
genotypes; the association was independent of sex. Furthermore,
the 825T allele frequency tended to be higher in subjects who took
antihypertensive medications than in subjects who did not (0.571 versus
0.496; P=NS), although this young sample had relatively
few subjects with hypertension. The findings support an association of
variation in this gene with variation in blood pressure.
Key Words: ion channels • hypertension, genetic • linkage disequilibrium • genetics
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