A common β1-adrencrgic receptor polymorphism (Arg389Gly) affects blood pressure response to β-blockade

G. G. Sofowora; V. Dishy; M. Muszkat; H. G. Xie; R. B. Kim; P. A. Harris; H. C. Prasad; D. W. Byrne; U. B. Nair; Alastair J.J. Wood; C. M. Stein

doi:10.1016/S0009-9236(02)17734-4

A common β₁-adrencrgic receptor polymorphism (Arg389Gly) affects blood pressure response to β-blockade

G. G. Sofowora, V. Dishy, M. Muszkat, H. G. Xie, R. B. Kim, P. A. Harris, H. C. Prasad, D. W. Byrne, U. B. Nair, Alastair J.J. Wood^*, C. M. Stein

^*Corresponding author for this work

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Abstract

Background: A common polymorphism of the β₁-adrenergic receptor Arg389Gly markedly affects function in vitro, but little is known about its in vivo significance. Methods and Results: Resting and exercise hemodynamic responses were measured in subjects homozygous for Arg389 (n = 21) or Gly389 (n = 13) alleles before and 3 hours after administration of a β-blocker, atenolol. Demographic characteristics and atenolol concentrations were similar in the two genotypic groups. Genotype had a marked effect on resting hemodynamic responses to atenolol, with Arg389-homozygous subjects having a larger decrease in resting systolic blood pressure (8.7 ± 1.3 mm Hg versus 0.2 ± 1.7 mm Hg, P < .001) and mean arterial blood pressure (7.2 ± 1.0 mm Hg versus 2.0 ± 1.7 mm Hg, P = .009). Attenuation of exercise-induced hemodynamic responses by atenolol was not affected by genotype. Conclusions: There is reduced sensitivity of Gly389 homozygotes to a β-adrenergic receptor antagonist, and this polymorphism may be an important determinant of variability in response to β-blockade.

Original language	English
Pages (from-to)	366-371
Number of pages	6
Journal	Clinical Pharmacology and Therapeutics
Volume	73
Issue number	4
DOIs	https://doi.org/10.1016/S0009-9236(02)17734-4
State	Published - 1 Apr 2003
Externally published	Yes

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title = "A common β1-adrencrgic receptor polymorphism (Arg389Gly) affects blood pressure response to β-blockade",

abstract = "Background: A common polymorphism of the β1-adrenergic receptor Arg389Gly markedly affects function in vitro, but little is known about its in vivo significance. Methods and Results: Resting and exercise hemodynamic responses were measured in subjects homozygous for Arg389 (n = 21) or Gly389 (n = 13) alleles before and 3 hours after administration of a β-blocker, atenolol. Demographic characteristics and atenolol concentrations were similar in the two genotypic groups. Genotype had a marked effect on resting hemodynamic responses to atenolol, with Arg389-homozygous subjects having a larger decrease in resting systolic blood pressure (8.7 ± 1.3 mm Hg versus 0.2 ± 1.7 mm Hg, P < .001) and mean arterial blood pressure (7.2 ± 1.0 mm Hg versus 2.0 ± 1.7 mm Hg, P = .009). Attenuation of exercise-induced hemodynamic responses by atenolol was not affected by genotype. Conclusions: There is reduced sensitivity of Gly389 homozygotes to a β-adrenergic receptor antagonist, and this polymorphism may be an important determinant of variability in response to β-blockade.",

author = "Sofowora, {G. G.} and V. Dishy and M. Muszkat and Xie, {H. G.} and Kim, {R. B.} and Harris, {P. A.} and Prasad, {H. C.} and Byrne, {D. W.} and Nair, {U. B.} and Wood, {Alastair J.J.} and Stein, {C. M.}",

year = "2003",

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doi = "10.1016/S0009-9236(02)17734-4",

language = "אנגלית",

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pages = "366--371",

journal = "Clinical Pharmacology and Therapeutics",

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T1 - A common β1-adrencrgic receptor polymorphism (Arg389Gly) affects blood pressure response to β-blockade

AU - Sofowora, G. G.

AU - Dishy, V.

AU - Muszkat, M.

AU - Xie, H. G.

AU - Kim, R. B.

AU - Harris, P. A.

AU - Prasad, H. C.

AU - Byrne, D. W.

AU - Nair, U. B.

AU - Wood, Alastair J.J.

AU - Stein, C. M.

PY - 2003/4/1

Y1 - 2003/4/1

N2 - Background: A common polymorphism of the β1-adrenergic receptor Arg389Gly markedly affects function in vitro, but little is known about its in vivo significance. Methods and Results: Resting and exercise hemodynamic responses were measured in subjects homozygous for Arg389 (n = 21) or Gly389 (n = 13) alleles before and 3 hours after administration of a β-blocker, atenolol. Demographic characteristics and atenolol concentrations were similar in the two genotypic groups. Genotype had a marked effect on resting hemodynamic responses to atenolol, with Arg389-homozygous subjects having a larger decrease in resting systolic blood pressure (8.7 ± 1.3 mm Hg versus 0.2 ± 1.7 mm Hg, P < .001) and mean arterial blood pressure (7.2 ± 1.0 mm Hg versus 2.0 ± 1.7 mm Hg, P = .009). Attenuation of exercise-induced hemodynamic responses by atenolol was not affected by genotype. Conclusions: There is reduced sensitivity of Gly389 homozygotes to a β-adrenergic receptor antagonist, and this polymorphism may be an important determinant of variability in response to β-blockade.

AB - Background: A common polymorphism of the β1-adrenergic receptor Arg389Gly markedly affects function in vitro, but little is known about its in vivo significance. Methods and Results: Resting and exercise hemodynamic responses were measured in subjects homozygous for Arg389 (n = 21) or Gly389 (n = 13) alleles before and 3 hours after administration of a β-blocker, atenolol. Demographic characteristics and atenolol concentrations were similar in the two genotypic groups. Genotype had a marked effect on resting hemodynamic responses to atenolol, with Arg389-homozygous subjects having a larger decrease in resting systolic blood pressure (8.7 ± 1.3 mm Hg versus 0.2 ± 1.7 mm Hg, P < .001) and mean arterial blood pressure (7.2 ± 1.0 mm Hg versus 2.0 ± 1.7 mm Hg, P = .009). Attenuation of exercise-induced hemodynamic responses by atenolol was not affected by genotype. Conclusions: There is reduced sensitivity of Gly389 homozygotes to a β-adrenergic receptor antagonist, and this polymorphism may be an important determinant of variability in response to β-blockade.

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A common β₁-adrencrgic receptor polymorphism (Arg389Gly) affects blood pressure response to β-blockade

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