The effect of common polymorphisms of the β2-adrenergic receptor on agonist-mediated vascular desensitization
The effect of common polymorphisms of the β2-adrenergic receptor on agonist-mediated vascular desensitization
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DOI：
10.1056/nejmoa010819
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发表时间：
2001-10-04
影响因子：
158.5
通讯作者：
Wood, AJJ
中科院分区：
文献类型：
--
作者：
Dishy, V;Sofowora, GG;Wood, AJJ
背景：随着持续暴露于β(2)-肾上腺素能激动剂，血管组织对激动剂介导的血管舒张变得脱敏。我们研究了β(2)-肾上腺素能受体的两种常见多态性，一个在密码子16上，一个在密码子27上，对激动剂介导的血管舒张和血管床脱敏的影响。方法：选取26名健康受试者，分别代表3种基因型：编码Arg16和GIn27的等位基因纯合子7例，编码Gly16和Gln27的等位基因纯合子8例，编码Gly16和Glu27的等位基因纯合子11例。通过测量手背静脉直径的变化来评估血管反应。构建β(2)-肾上腺素能受体激动剂异丙肾上腺素作用的剂量-反应曲线（剂量范围为4 ~ 480 ng / min）。然后通过持续输注异丙肾上腺素2小时诱导脱敏，并在输注开始后30、60、90和120分钟测量静脉扩张。结果：Arg16纯合的受试者几乎完全脱敏；该组对异丙肾上腺素反应的静脉扩张从平均（+/-SE） 44+/- 11%下降到8+/- 4% （P=0.006）。相比之下，Gly16纯合子的受试者没有明显的脱敏，与密码子27编码的氨基酸无关。与Gln27纯合子的受试者相比，gl27纯合子的受试者对异丙肾上腺素的最大静脉扩张率更高（86+/- 13%比54+/- 8%，P=0.03）。结论：β(2)-肾上腺素能受体Arg16多态性与血管中激动剂介导的脱敏增强有关，Glu27多态性与激动剂介导的反应性增强有关。因此，β(2)-肾上腺素能受体的多态性可能是血管应激反应的重要决定因素。[J] .中华医学杂志，2001;35(5):559 - 559。版权所有(C) 2001马萨诸塞州医学协会。
Background: With continuous exposure to beta (2)-adrenergic agonists, vascular tissue becomes desensitized to agonist-mediated vasodilatation. We studied the effects of two common polymorphisms of the beta (2)-adrenergic receptor, one at codon 16 and one at codon 27, on agonist-mediated vasodilatation and desensitization in the vascular bed.Methods: We studied 26 healthy subjects who were selected to represent three genotypes: 7 were homozygous for the alleles encoding Arg16 and GIn27, 8 were homozygous for the alleles encoding Gly16 and Gln27, and 11 were homozygous for the alleles encoding Gly16 and Glu27. Vascular responses were assessed by measuring changes in the diameter of a dorsal hand vein. A dose-response curve of the effect of the beta (2)-adrenergic-receptor agonist isoproterenol was constructed (dose range, 4 to 480 ng per minute). Desensitization was then induced by a 2-hour continuous infusion of isoproterenol, and venodilatation was measured 30, 60, 90, and 120 minutes after the start of the infusion.Results: Subjects who were homozygous for Arg16 had almost complete desensitization; venodilatation in response to isoproterenol in this group decreased from a mean (+/-SE) of 44+/-11 percent to 8+/-4 percent (P=0.006). In contrast, subjects who were homozygous for Gly16 did not have significant desensitization, irrespective of the amino acid encoded by codon 27. Subjects who were homozygous for Glu27 had higher maximal venodilatation in response to isoproterenol than those who were homozygous for Gln27 (86+/-13 percent vs. 54+/-8 percent, P=0.03).Conclusions: The Arg16 polymorphism of the beta (2)-adrenergic receptor is associated with enhanced agonist-mediated desensitization in the vasculature, and the Glu27 polymorphism is associated with increased agonist-mediated responsiveness. Therefore, polymorphisms of the beta (2)-adrenergic receptor are potentially important determinants of the vascular response to stress. (N Engl J Med 2001;345:1030-5.) Copyright (C) 2001 Massachusetts Medical Society.