17q21 variant increases the risk of exacerbations in asthmatic children despite inhaled corticosteroids use

Approximately 25% of the asthmatic children suffer from uncontrolled asthma despite regular use of inhaled corticosteroids (ICS).1 Variation within the 17q21 locus is the strongest genetic determinant for childhood‐onset asthma.2 Recently, the influence of this locus on treatment outcomes has been shown in several studies.3, 4 The Pharmacogenomics in Childhood Asthma (PiCA) consortium is a multiethnic consortium that brings together data from ≥14 000 asthmatic children/young adults from 12 different countries to study the pharmacogenomics of uncontrolled asthma despite treatment.5 In 14 PiCA populations (with over 4000 asthmatic patients), we studied the association between variation in the 17q21 locus, and asthma exacerbations despite ICS use. We specifically focused on rs7216389, a single nucleotide polymorphism (SNP) in the 17q21 locus strongly associated with childhood asthma and initially identified by Moffatt et al.2 Ten PiCA studies included patients with non‐Hispanic European origins, two included Hispanic patients, one African American, and one included East Asian patients. Additional details of the study populations can be found in the Data S1. Two outcomes were assessed: (i) asthma‐related hospitalizations/emergency department visit (ED) visits and (ii) short courses of oral corticosteroid (OCS) use reported by the parent/child at the study visit or based on completed study questionnaires. Age, gender, genotype data, and exacerbation data were available for 4529 steroid‐treated children and young adults (Table 1). Logistic regression analysis was used to assess the risk of exacerbations when carrying rs7216389. Due to potential heterogeneity between cohorts, the odds ratios (ORs) were meta‐analyzed with the inverse variance weighting method assuming random effects. See Data S1 for more detail.