肾上腺素能受体从实验室到床边的药物基因组学:在重症监护中的潜在临床意义

Jude Howaidi, H. Lababidi
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引用次数: 0

摘要

α和β肾上腺素能受体相关基因的DNA序列差异可导致遗传多态性。这些变异可能潜在地影响对肾上腺素能激动剂和拮抗剂治疗的反应,可能需要医疗干预。药物基因组学的概念是“把合适的药物给合适的病人”,这意味着药物基因组学是完全个性化的。鉴于肾上腺素受体在儿茶酚胺与α和β肾上腺素能受体之间的药理学相互作用中起着重要作用,因此,强调并进一步分析肾上腺素能受体之间的变异,以改善儿茶酚胺功能障碍相关疾病的管理是至关重要的。在这篇综述中,我们强调了肾上腺素能受体的药物基因组学及其在重症监护中的潜在临床意义。结果表明,在不同人群和种族中,肾上腺素能受体α - 1A (ADRA1A)、肾上腺素能受体α - 2A (ADRA2A)、肾上腺素能受体β -1 (ADRB1)和肾上腺素能受体β -2基因存在多种变异,包括ADRA1A和ADRB1中的Arg347Cys和Arg389Gly基因。这些多态性导致了肾上腺素、右美托咪定和沙丁胺醇的药物反应的个体间差异,这表明肾上腺素能受体的药物基因组学已经证明了候选基因在导致不同药物反应的人群中的巨大差异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pharmacogenomics of adrenergic receptors from bench to bedside: Potential clinical implications in critical care
Distinctions in the DNA sequence of the genes pertaining to α and β adrenergic receptors can result in genetic polymorphisms. These variations can potentially impact response to treatment with adrenergic agonists and antagonists that likely warrant medical intervention. Pharmacogenomics is conceptualized as “the right drug to the right patient,” which implies that pharmacogenomics is entirely personalized. Given that adrenoreceptors play a fundamental role in regards to the pharmacogenetic interaction between catecholamines with α and β adrenergic receptors, it is, therefore, pivotal to highlight and further analyze variants amongst adrenergic receptors to improve the management of diseases pertaining to catecholamine dysfunction. In this review, we highlight the pharmacogenomics of adrenergic receptors and their potential clinical implications in critical care. It is evident that there are several variants associated with the adrenergic receptor alpha 1A (ADRA1A), adrenergic receptor alpha 2A (ADRA2A), adrenergic receptor beta-1 (ADRB1), adrenergic receptor beta-2 genes for α and β adrenergic receptors that were observed among different populations and ethnic groups including the Arg347Cys and Arg389Gly in ADRA1A and ADRB1, respectively. These polymorphisms have resulted in interindividual variability in drug responses for epinephrine, dexmedetomidine, and salbutamol, which concludes that pharmacogenomics of adrenergic receptors have proven immense variability in candidate genes amongst populations that lead to different drug responses.
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