Human β2-adrenergic receptor polymorphisms:: No association with essential hypertension in black or white Americans

被引:70
作者
Xie, HG [1 ]
Stein, CM
Kim, RB
Gainer, JV
Sofowora, G
Dishy, V
Brown, NJ
Goree, RE
Haines, JL
Wood, AJJ
机构
[1] Vanderbilt Univ, Sch Med, Dept Med, Div Clin Pharmacol, Nashville, TN 37212 USA
[2] Vanderbilt Univ, Sch Med, Dept Pharmacol, Div Clin Pharmacol, Nashville, TN 37212 USA
[3] Vanderbilt Univ, Sch Med, Program Human Genet, Nashville, TN 37212 USA
[4] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA
关键词
D O I
10.1067/mcp.2000.106293
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background and Objectives: The most common polymorphisms of the human beta(2)-adrenergic receptor - Arg16 --> Gly and Gln27 --> Glu - are associated with alterations in beta(2)-adrenergic receptor responses, both in vitro and in vivo. beta(2)-Adrenergic receptor-mediated vascular responses are affected by ethnicity, blood pressure, and genotype. We tested the hypothesis that these two common beta(2)-adrenergic receptor genetic variants are associated with essential hypertension in black or white Americans. Subjects and Methods: In a population-based case-control association study, the relationship between beta(2)-adrenergic receptor genotypes and hypertension was examined in 307 normotensive subjects (128 black and 179 white) and 356 hypertensive subjects (155 black and 201 white). A polymerase chain reaction-based single-stranded conformational polymorphism method with direct sequencing of the bands of interest was used to detect the two frequently occurring beta(2)-adrenergic receptor variants (Arg16-->Gly, Gln27-->Glu). Results: No significant differences in the distributions of alleles and genotypes of the tested beta(2)-adrenergic receptor variants were found between normotensive and hypertensive groups from either black or white Americans (all P >.05). There was a marked interethnic difference in the frequency of the Gln27-->Glu beta(2)-adrenergic receptor polymorphism in both normotensive and hypertensive subjects. Ln normotensive white: subjects, the variant Glu27 allele (35.2% versus 18.0%; P <.0001) and Glu27 homozygous genotype (14.0% versus 4.7%; P <.01) mere more common than in black subjects. Similarly, in hypertensive white subjects, the variant Glu27 allele (35.8% versus 18.4%; P <.0001) and the Glu27 homozygous genotype (15.9% ret sus 2.6%; P <.0001) were more common than in black subjects. Conclusions: These data suggest that although there are marked ethnic differences in their distribution, the common genetic polymorphisms of the human beta(2)-adrenergic receptor gene do not cosegregate with the presence of hypertension in either black or white Americans.
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页码:670 / 675
页数:6
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