GENETIC VARIATION IN THE β(2)-ADRENERGIC RECEPTOR: IMPACT ON INTERMEDIATE CARDIOVASCULAR PHENOTYPES.
GENETIC VARIATION IN THE β(2)-ADRENERGIC RECEPTOR: IMPACT ON INTERMEDIATE CARDIOVASCULAR PHENOTYPES.
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DOI：
10.2174/1875692110806030160
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发表时间：
2008-09
影响因子：
--
通讯作者：
Eisenach JH
中科院分区：
文献类型：
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作者：
Hesse C;Eisenach JH
药物靶点（例如受体）的遗传变异可能对内源性和外源性激动剂的临床反应产生显着影响。编码 β2 肾上腺素受体 (β2-AR) 的基因多态性与体外表达改变、下调和细胞信号传导改变有关。由于β2-AR在心血管系统的调节中发挥着至关重要的作用，β2-AR遗传变异对心血管对生理或药理刺激反应的功能重要性已引起广泛关注。本综述的目的是描述这些中间心血管表型及其对心血管疾病和肾上腺素能药物反应的影响。 β2-AR 基因密码子 46 (Gly16Arg) 和 79 (Gln27Glu) 编码的两种常见单核苷酸多态性已得到深入研究。它们已被证明与局部和全身给予β2激动剂的血管舒张反应改变、交感兴奋性运动的心血管反应改变以及心肌功能改变有关。重要的是，这些中间生理模式可能会影响高血压和其他心血管疾病的发展和相关结果。正如最近报道的，β2-AR 基因变异可以对接受 β 受体阻滞剂治疗的患者进行风险分层，并可以预测 β 受体阻滞剂对急性冠脉综合征患者或心力衰竭患者的疗效。进一步的研究将加深我们对 β2-AR 基因型、中间心血管表型和临床表型之间联系的理解。从长远来看，应重新评估基因型组内β受体阻滞剂治疗的益处，最终目标是为个体患者设计最佳治疗方案。
Genetic variation in drug targets (e.g. receptors) can have pronounced effects on clinical responses to endogenous and exogenous agonists. Polymorphisms in the gene encoding the β2-adrenergic receptor (β2-AR) have been associated with altered expression, down-regulation, and altered cell signaling in vitro. Because β2-ARs play a crucial role in the regulation of the cardiovascular system, the functional importance of genetic variation in the β2-AR on cardiovascular responses to physiological or pharmacological stimuli has gained widespread attention. The objective of this review is to characterize these intermediate cardiovascular phenotypes and their influence on cardiovascular disease and adrenergic drug responses. Two common single nucleotide polymorphisms, encoded at codon 46 (Gly16Arg) and 79 (Gln27Glu) of the β2-AR gene, have been studied intensively. They have been shown to be associated with altered vasodilator responses to regional and systemic administration of β2-agonists, altered cardiovascular responses to sympathoexcitatory maneuvers, and altered myocardial function. Importantly, these intermediate physiological patterns may influence the development of and the outcomes associated with hypertension and other cardiovascular diseases. As recently reported, β2-AR gene variation can risk-stratify patients receiving β-blocker therapy and may predict β-blocker efficacy in patients post acute coronary syndrome or in patients with heart failure. Further studies will advance our understanding of the link between β2-AR genotypes, intermediate cardiovascular phenotypes, and clinical phenotypes. In the long term, reassessment of the benefits of β-blocker-therapy within genotype groups should be carried out with the ultimate goal to design the optimal therapeutic regimen for the individual patient.