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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
- 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.
- Subjects :
- Genetic Markers
Male
Risk
medicine.medical_specialty
Genotype
Hydrocortisone
medicine.drug_class
Disease
Mean airway pressure
Polymorphism, Single Nucleotide
Receptors, Corticotropin-Releasing Hormone
Article
Dexamethasone
law.invention
03 medical and health sciences
Surface-Active Agents
0302 clinical medicine
Randomized controlled trial
law
Adrenal Cortex Hormones
030225 pediatrics
Internal medicine
medicine
Humans
Glucocorticoids
Bronchopulmonary Dysplasia
business.industry
Infant, Newborn
medicine.disease
Introns
Phenotype
Bronchopulmonary dysplasia
Pharmacogenetics
Pediatrics, Perinatology and Child Health
Multivariate Analysis
Corticosteroid
Female
business
030217 neurology & neurosurgery
Infant, Premature
medicine.drug
Subjects
Details
- ISSN :
- 15300447
- Volume :
- 85
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Pediatric research
- Accession number :
- edsair.doi.dedup.....8a477079cfe07589b035a85236e16cfb