Pharmacogenomics of adrenergic receptors from bench to bedside: Potential clinical implications in critical care

Abstract

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.