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

Creator(s)

Tamorah R. Lewis MD PhD, Children's Mercy HospitalFollow
William E. Truog, Children's Mercy HospitalFollow
Michael Norberg, Children's Mercy HospitalFollow
Philip L. Ballard
Dara Torgerson
TOLSURF Study Group

Document Type

Article

Publication Date

4-2019

Identifier

DOI: 10.1038/s41390-018-0235-1; PMCID: PMC6532775

Abstract

Background: Bronchopulmonary dysplasia (BPD) is an orphan disease and advances in prevention and treatment are lacking. The 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 a change in respiratory severity score (RSS, mean airway pressure x 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.

Conclusions: 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.

Journal Title

Pediatric research

Volume

85

Issue

5

First Page

625

Last Page

633

Comments

Grant support

• U01 HL094338/HL/NHLBI NIH HHS/United States

Erratum in

• Correction: Genetic variation in CRHR1 is associated with short-term respiratory response to corticosteroids in preterm infants at risk for bronchopulmonary dysplasia. Lewis T, Truog W, Norberg M, Ballard PL, Torgerson D; TOLSURF Study Group.Pediatr Res. 2019 Apr;85(5):731. doi: 10.1038/s41390-019-0314-y.PMID: 30733615
• In the original version of this article, the Supplementary Information file contained incorrect reference numbers. 'Supplemental Table S1' has now been replaced with the corrected version, in which the correct reference numbers are cited. The authors would like to apologise for this error.

Recommended Citation

Lewis T, Truog W, Norberg M, Ballard PL, Torgerson D; TOLSURF Study Group. Genetic variation in CRHR1 is associated with short-term respiratory response to corticosteroids in preterm infants at risk for bronchopulmonary dysplasia [published correction appears in Pediatr Res. 2019 Feb 7;:]. Pediatr Res. 2019;85(5):625-633. doi:10.1038/s41390-018-0235-1