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Genetic variation in CRHR1 is associated with short-term respiratory response to corticosteroids in preterm infants at risk for bronchopulmonary dysplasia

Authors :
William E Truog
Dara G. Torgerson
Tamorah R Lewis Md PhD
Philip L. Ballard
Michael Norberg
Source :
Pediatric research
Publication Year :
2018

Abstract

Background Bronchopulmonary Dysplasia (BPD) is an orphan disease and advances in prevention and treatment are lacking. Clinical efficacy of systemic corticosteroid therapy to reduce the severity of lung disease and BPD is highly variable. Our objective was to assess whether candidate SNPs in corticosteroid metabolism and response genes are associated with short-term phenotypic response to systemic corticosteroids in infants at high risk for BPD. Methods Pharmacogenetic analysis of data from a large randomized controlled trial (TOLSURF) in infants treated with dexamethasone or hydrocortisone using multivariate linear regression. The primary outcome was change in Respiratory Severity Score (RSS, mean airway pressure × FiO2) at day 7 of corticosteroid treatment. Results rs7225082 in the intron of CRHR1 is significantly associated with the magnitude of decrease in RSS 7 days after starting treatment with systemic corticosteroid (meta-analysis p=2.8×10−4). Each T allele at rs7225082 is associated with a smaller absolute change in RSS at day 7, i.e. less response to systemic corticosteroids. Conclusion Genetic variability is associated with corticosteroid responsiveness with regard to respiratory status in preterm infants. Identification of genetic markers of corticosteroid responsiveness may allow for therapeutic individualization, with the goal of optimizing the risk to benefit ratio for an individual child.

Details

ISSN :
15300447
Volume :
85
Issue :
5
Database :
OpenAIRE
Journal :
Pediatric research
Accession number :
edsair.doi.dedup.....8a477079cfe07589b035a85236e16cfb