Abstract
Background: Genetic variation has been associated with altered corticosteroid response in asthmatic patients.
Aim: To study whether variation in 17 candidate genes is associated with exacerbations in asthmatic children and adolescents treated with inhaled corticosteroids (ICS).
Material and methods: We performed a meta-analysis of 4 studies: the PACMAN study (n=357, age: 4-12, NL), the BREATHE study (n=818, age: 3-22, UK), the PAGES study (n=391, age: 2-16, UK) and the CAMP trial (n=172, age: 5-12, USA). Genes were selected based on their role in the glucocorticoid signaling pathway or a previously reported association with asthma. Fifty SNPs were screened. As outcomes we studied: 1) asthma-related hospital visits, 2) oral corticosteroid (OCS) use in the previous year. Odds ratios (OR) were corrected for age, sex and treatment step and meta-analyzed assuming random effects with the inverse variance weighting method. Q-values were calculated to correct for multiple testing.
Results: We found two SNPs in ST13 to be associated with both outcomes. ST13 rs138335 C-allele was associated with a decreased risk of exacerbations (OCS use OR: 0.78, 95%CI:0.65-0.91, p=0.003, q=0.05; hospital visits OR: 0.78, 95%CI: 0.63-0.97, p=0.02, q=0.45). The G-allele of rs138337 ST13 was associated with an increased risk (OCS use OR:1.18, 95%CI:1.01-1.38, p=0.03, q=0.31; hospital visits OR: 1.30, 95%CI:1.07-1.58, p=0.007, q=0.28). Furthermore, the C-allele of rs7216389 ORMDL3 was associated with fewer OCS use in the previous year (OR: 0.77, 95%CI:0.62-0.95, p=0.02, q=0.05).
Conclusion: ST13 and ORMDL3 seem to be associated with altered risk of asthma exacerbations despite ICS treatment.
- © 2013 ERS
