Pharmacogenetic Factors Affecting Asthma Treatment Response. Potential Implications for Drug Therapy

Abstract

Asthma is a frequent disease, mainly characterized by airway inflammation, in which drug therapy is crucial in its management. The potential of pharmacogenomics testing in asthma therapy has been, to date, little explored. In this review, we discuss pharmacogenetic factors affecting asthma treatment, both related to drugs used as controller medications for regular maintenance, such as inhaled corticosteroids, anti-leukotriene agents, long-acting beta-agonists, and the new biologic agents used to treat severe persistent asthma. In addition, we discuss current pharmacogenomics knowledge for rescue medications provided to all patients for as-needed relief, such as short-acting beta-agonists. Evidence for genetic variations as a factor related to drugs response has been provided for the following genes and groups of drugs: Inhaled corticosteroids: FCER2 ; anti-leukotriene agents: ABCC1 , and LTC4S ; beta-agonists: ADRB2 . However, the following genes require further studies confirming or rejecting association with the response to asthma therapy: ADCY9, ALOX5, ARG1, ARG2, CRHR1, CRHR2, CYP3A4, CYP3A5, CYSLTR1, CYSLTR2, GLCCI1, IL4RA, LTA4H, ORMDL3, SLCO2B1, SPATS2L, STIP1, T, TBX21, THRA, THRB , and VEGFA . Although only a minority of these genes are, at present, listed as associated with drugs used in asthma therapy, in the Clinical Pharmacogenomics Implementation Consortium gene-drug pair list, this review reveals that sufficient evidence to start testing the potential of clinical pharmacogenomics in asthma therapy already exists. This evidence supports the inclusion in pilot pharmacogenetics tests of at least four genes. Hopefully these tests, if proven useful, will increase the efficiency and the safety of asthma therapy.

<p>Pharmacogenetics of Pediatric Asthma: Current Perspectives</p>

“…32,36,40,73,74,79 During this period, candidate-gene studies reported the association of genes previously described in pharmacogenetic studies of pediatric asthma with treatment response (ADRB2, GSDMB, FCER2, and VEGFA). 13,[16][17][18] Additionally, other candidate genes have been related for the first time to this phenotype in children (SPATS2L, ASB3, IL1RL1, MMP9, and COL2A1). Although several findings support previous evidence of some of these genes in asthma treatment response, inconsistent results across the literature or even across the studies included in this review have been found.…”

“…ADRB2 gene has been the most studied candidate gene of SABA response. 16,18,23 It encodes the β 2 adrenergic receptor, which is implicated in the bronchodilation process and is the biological target of β 2 adrenergic agonists. 19 In fact, in the reviewed period four candidate-gene studies have assessed the effect of the SNPs rs1042713 (arginine to glycine [Arg16Gly]) and rs1042714 (glutamic acid to glutamine [Glu27Gln]) on changes in lung function after SABA administration in European 24,25 and Egyptian 26,27 populations (Table 1).…”

“…26,[54][55][56][57][58][59] Similarly to the response to SABA, the ADRB2 gene is one of the most extensively analyzed in pharmacogenetic studies of ICS. 16,18,23 In 2018, Sood et al 54 studied two SNPs (rs1042713 and rs1042714) from the ADRB2 gene in a European American and African American cohort (n=373) of children with asthma under ICS treatment. In this study, treatment response was defined as the prescription of systemic corticosteroids due to asthma exacerbations in the last 12 months.…”

“…12 The evidence of the role of genetic variants on asthma treatment response has been summarized in some recent reviews. [13][14][15][16][17][18] Thereby, this review aims to update the current findings described in pharmacogenetic studies of pediatric asthma published from 2018 through 2019.…”

Precision Medicine in Childhood Asthma: Omic Studies of Treatment Response

“…In the last year, the role of different omics in asthma treatment response has been recapitulated in different reviews [16][17][18][19][20][21]. This review aims to provide an update on the latest findings in omic studies of pediatric asthma treatment response.…”