Pharmacogenetic approaches in the treatment of asthma

Abstract

A patient's response to asthma therapy is determined by both genetic and environmental factors. In the past 10 years, we have witnessed significant progress in the field of asthma pharmacogenetics--the study of how a patient's genetic background determines the efficacy and potential for adverse effects to current asthma medication. There are now clear examples of gene polymorphisms that can influence responses to beta(2)-agonists, glucocorticosteroids, and leukotriene modifier drugs, the three main classes of medication used clinically to treat asthma. Identification of genetic polymorphism that predicts drug responses has the potential to lead to the development of new therapeutics, improve asthma management, and reduce serious episodes and hospitalizations. In this review, we discuss the current understanding of asthma pharmacogenetics, focusing on the main three classes of drugs currently used clinically.

Genetic basis for personalized medicine in asthma

“…In the next sections we provide an update on the pharmacogenetic aspects of current asthma medication and focus on more recent findings. For a comprehensive review of earlier studies of the pharmacogenetics of these drug classes see reviews [11][12][13][14][15].…”

“…Therefore, a common consensus on the contribution of Arg16 has yet to be reached. At least 12 different haplotypes (a specific combination of SNPs across the gene) have been described in the ADRB2 gene [18], which may explain the lack of consensus examining genotype effects in isolation [11]. Interestingly, recent GWA studies have failed to identify a signal to ADRB2 suggesting this gene is not a major asthma susceptibility gene [4][5][6][7][8][9].…”

“…Enhanced agonist-mediated receptor downregulation of the Gly16 variant and resistance to downregulation of the Glu27 variant were also observed (reviewed in [11,12,14,15]). A recent study did not identify a significant effect of the common ADRB2 coding region polymorphisms on responses to a range of b 2 -adrenergic receptor agonists, including indacaterol in vitro [19].…”

Implications of Pharmacogenomics in the Current and Future Treatment of Asthma

“…10 The highly complex respiratorys ystem is an important pathway for the entryo fd isease-causing vectors, including viruses, bacteria, fungi, toxins, and antigens. 11 Interpatient variability in response to treatments for respiratorydiseases, such as asthma, is veryh igh, 12,13 but efforts to understand potential genetic sources of this variability have lagged behind those for other conditions. The objective of this review is to highlight the pharmacogenomics of asthma and how they impact the medications utilized to treat this disease.…”

Genetic Bases for Predisposition to Common Multifactorial Disease in Man. Part II

“…Signaling through beta2-adrenergic receptors mediates numerous airway functions by regulating broncho-constriction and dilation pathways. Therefore, understanding these pathways may assist in defi ning the variability in therapeutic responses for beta2-agonists (6,64).…”