Genetic variation in CRHR1 is associated with short-term respiratory response to corticosteroids in preterm infants at risk for bronchopulmonary dysplasia
| Autor: | William E Truog, Dara G. Torgerson, Tamorah R Lewis Md PhD, Philip L. Ballard, Michael Norberg |
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| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | Pediatric research |
| ISSN: | 1530-0447 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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