ST13 polymorphisms and their effect on exacerbations in steroid-treated asthmatic children and young adults.



(2015) ST13 polymorphisms and their effect on exacerbations in steroid-treated asthmatic children and young adults. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 45 (6). pp. 1051-9. ISSN 1365-2222

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Abstract

Background: The clinical response to inhaled corticosteroids (ICS) is associated with single nucleotide polymorphisms (SNPs) in various genes. This study aimed to relate variations in genes in the steroid pathway and asthma susceptibility genes to exacerbations in children and young adults treated with ICS. Methods: We performed a meta-analysis of three cohort studies: PACMAN (n=357, age: 4-12 years, the Netherlands), BREATHE (n=820, age: 3-22 years, UK) and PAGES (n=391, age: 2-16 years, UK). Seventeengenes were selected based on a role in the glucocorticoid signaling pathway or a reported association with asthma. Two outcome parameters were used to reflect exacerbations: hospital visits and oral corticosteroid (OCS) use in the previous year. The most significant associations were tested in three independent validation cohorts; CAMP (clinical trial, n=172, age:5-12 years, USA), GALA II (n=745, age:8-21, USA) and the PASS cohort (n=391, age:5-18, UK)) to test the robustness of the findings. Finally, all results were meta-analyzed. Results: Two SNPs in ST13 (rs138335 and rs138337) were associated at a nominal level with an increased risk of exacerbations despite corticosteroid treatment in the three cohort studies. In a meta-analysis of all six studies ST13 rs138335 remained associated with an increased risk of asthma-related hospital visits; OR=1.22 per G allele for rs138335 (p=0.013) and an increased risk of OCS usage in the previous year (OR=1.22 per G allele for rs138337 (p=0.0017). Conclusion and clinical relevance: A novel susceptibility gene, ST13, coding for a co-chaperone of the glucocorticoid receptor, is associated with exacerbations in asthmatic children and young adults. Genetic variation in the glucocorticoid signaling pathway seems to add to the interindividual variability in clinical response to ICS treatment in children and young adults

Item Type: Article
Subjects: R Medicine > RJ Pediatrics
R Medicine > RJ Pediatrics > RJ101 Child Health. Child health services
R Medicine > RM Therapeutics. Pharmacology
Depositing User: Symplectic Admin
Date Deposited: 13 Jan 2016 10:32
Last Modified: 31 Mar 2016 12:46
URI: http://livrepository.liverpool.ac.uk/id/eprint/2042303
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