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(Circulation. 2000;101:2877.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Positional Genomic Analysis Identifies the ß2-Adrenergic Receptor Gene as a Susceptibility Locus for Human Hypertension
From the Institute of Molecular Medicine (M.S.B., J.K., L.L., E.B.) and Human Genetics Center (M.S.B., E.B.), The University of Texas–Houston Health Science Center, Houston, Tex; the Department of Human Genetics (R.F.), Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pa; the Departments of Epidemiology (S.K.) and Human Genetics (C.F.S.), University of Michigan, Ann Arbor, Mich; and the Division of Hypertension and Department of Internal Medicine (S.T.T.), Mayo Clinic, Rochester, Minn.
Correspondence to Eric Boerwinkle, PhD, Human Genetics Center, The University of Texas–Houston Health Science Center, PO Box 20334, Houston, TX 77225. E-mail eboerwin{at}gsbs.gs.uth.tmc.edu
Background—After genome-wide linkage analyses of blood pressure levels, we resequenced 5 positional candidate genes in a linkage region on chromosome 5 and genotyped selected variants in several family samples from Rochester, Minn.
Methods and Results—In a sample of 55 pedigrees containing 
1
sibling-pair(s) discordant for systolic blood pressure,
polymorphisms within the ß2-adrenergic receptor
gene (Arg16Gly, P=0.009) and the glutathione
peroxidase 3 gene (-302G
A, P=0.037; -623AC,
P=0.013) were significantly related to blood pressure
levels. In a second sample of 298 nuclear families (n=1283
individuals), the Arg16Gly polymorphism was significantly
associated with diastolic blood pressure in family-based
analyses (P=0.016) and with both
diastolic (P=0.009) and mean
arterial blood pressure (P=0.038) in
analyses of the parental generation only. Neither
polymorphism in the glutathione peroxidase 3 gene was associated
with blood pressure levels in this sample. An additional 291 families
(n=1240 individuals) were added to the nuclear family sample, and the
Gln27Glu polymorphism in the ß2-adrenergic receptor
gene was significantly associated with both systolic
(P=0.034) and mean arterial blood pressure
(P=0.035) in the parental generation of the combined 589
families. The frequencies of both the Gly16 and Glu27 alleles were
higher in hypertensives than in normotensives (0.649 versus 0.604 and
0.490 versus 0.429, respectively), and the odds ratio for the
occurrence of hypertension was 1.80 (95% confidence interval, 1.08 to
3.00; P=0.023) for the Glu27 allele.
Conclusions—The results of this study provide support for further detailed investigations of the mechanistic pathways by which variations in the ß2-adrenergic receptor gene may influence blood pressure levels.
Key Words: linkage (genetics) • genetics • polymorphism (genetics) • blood pressure
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