Positional genomic analysis identifies the β2-adrenergic receptor gene as a susceptibility locus for human hypertension

Molly S. Bray, Julia Krushkal, Li Li, Robert Ferrell, Sharon Kardia, Charles F. Sing, Stephen T Turner, Eric Boerwinkle

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

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 β2-adrenergic receptor gene (Arg16Gly, P=0.009) and the glutathione peroxidase 3 gene (-302G→A, P=0.037; -623A→C, 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 β2-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 β2- adrenergic receptor gene may influence blood pressure levels.

Original languageEnglish (US)
Pages (from-to)2877-2882
Number of pages6
JournalCirculation
Volume101
Issue number25
StatePublished - Jun 27 2000

Fingerprint

Adrenergic Receptors
Blood Pressure
Hypertension
Genes
Arterial Pressure
Glutathione Peroxidase
Nuclear Family
Alleles
Chromosomes, Human, Pair 5
Pedigree
Siblings
Odds Ratio
Genome
Confidence Intervals

Keywords

  • Blood pressure
  • Genetics
  • Linkage (genetics)
  • Polymorphism (genetics)

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Bray, M. S., Krushkal, J., Li, L., Ferrell, R., Kardia, S., Sing, C. F., ... Boerwinkle, E. (2000). Positional genomic analysis identifies the β2-adrenergic receptor gene as a susceptibility locus for human hypertension. Circulation, 101(25), 2877-2882.

Positional genomic analysis identifies the β2-adrenergic receptor gene as a susceptibility locus for human hypertension. / Bray, Molly S.; Krushkal, Julia; Li, Li; Ferrell, Robert; Kardia, Sharon; Sing, Charles F.; Turner, Stephen T; Boerwinkle, Eric.

In: Circulation, Vol. 101, No. 25, 27.06.2000, p. 2877-2882.

Research output: Contribution to journalArticle

Bray, MS, Krushkal, J, Li, L, Ferrell, R, Kardia, S, Sing, CF, Turner, ST & Boerwinkle, E 2000, 'Positional genomic analysis identifies the β2-adrenergic receptor gene as a susceptibility locus for human hypertension', Circulation, vol. 101, no. 25, pp. 2877-2882.
Bray MS, Krushkal J, Li L, Ferrell R, Kardia S, Sing CF et al. Positional genomic analysis identifies the β2-adrenergic receptor gene as a susceptibility locus for human hypertension. Circulation. 2000 Jun 27;101(25):2877-2882.
Bray, Molly S. ; Krushkal, Julia ; Li, Li ; Ferrell, Robert ; Kardia, Sharon ; Sing, Charles F. ; Turner, Stephen T ; Boerwinkle, Eric. / Positional genomic analysis identifies the β2-adrenergic receptor gene as a susceptibility locus for human hypertension. In: Circulation. 2000 ; Vol. 101, No. 25. pp. 2877-2882.
@article{91d8b611fbf04436b8baebba2ab84c12,
title = "Positional genomic analysis identifies the β2-adrenergic receptor gene as a susceptibility locus for human hypertension",
abstract = "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 β2-adrenergic receptor gene (Arg16Gly, P=0.009) and the glutathione peroxidase 3 gene (-302G→A, P=0.037; -623A→C, 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 β2-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 β2- adrenergic receptor gene may influence blood pressure levels.",
keywords = "Blood pressure, Genetics, Linkage (genetics), Polymorphism (genetics)",
author = "Bray, {Molly S.} and Julia Krushkal and Li Li and Robert Ferrell and Sharon Kardia and Sing, {Charles F.} and Turner, {Stephen T} and Eric Boerwinkle",
year = "2000",
month = "6",
day = "27",
language = "English (US)",
volume = "101",
pages = "2877--2882",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "25",

}

TY - JOUR

T1 - Positional genomic analysis identifies the β2-adrenergic receptor gene as a susceptibility locus for human hypertension

AU - Bray, Molly S.

AU - Krushkal, Julia

AU - Li, Li

AU - Ferrell, Robert

AU - Kardia, Sharon

AU - Sing, Charles F.

AU - Turner, Stephen T

AU - Boerwinkle, Eric

PY - 2000/6/27

Y1 - 2000/6/27

N2 - 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 β2-adrenergic receptor gene (Arg16Gly, P=0.009) and the glutathione peroxidase 3 gene (-302G→A, P=0.037; -623A→C, 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 β2-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 β2- adrenergic receptor gene may influence blood pressure levels.

AB - 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 β2-adrenergic receptor gene (Arg16Gly, P=0.009) and the glutathione peroxidase 3 gene (-302G→A, P=0.037; -623A→C, 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 β2-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 β2- adrenergic receptor gene may influence blood pressure levels.

KW - Blood pressure

KW - Genetics

KW - Linkage (genetics)

KW - Polymorphism (genetics)

UR - http://www.scopus.com/inward/record.url?scp=0034720848&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034720848&partnerID=8YFLogxK

M3 - Article

C2 - 10869257

AN - SCOPUS:0034720848

VL - 101

SP - 2877

EP - 2882

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 25

ER -