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Glucocorticoid Receptor Gene Variants and Neonatal Outcome in Very-Low-Birth-Weight Preterm Infants
Christine Schreiner1, Felix Schreiner, Christoph Härtel
1Department of Neonatology, Children's Hospital, University of Bonn, Bonn, Germany.
Insights
Glucocorticoid receptor (GR) gene polymorphisms, specifically BclI, were linked to an increased risk of bronchopulmonary dysplasia in very-low-birth-weight infants. Other GR gene variants did not significantly impact neonatal outcomes in this large study.
Area of Science:
- Neonatal Medicine
- Genetics
- Pharmacogenomics
Background:
- Prenatal steroid treatment is standard for preterm birth to improve lung maturation and reduce neonatal complications.
- Interindividual differences in corticosteroid sensitivity due to glucocorticoid receptor (GR) gene polymorphisms are not well understood.
- Investigating GR gene variants may reveal factors influencing treatment response and neonatal outcomes.
Purpose of the Study:
- To evaluate the impact of specific GR gene polymorphisms (N363S, R23K, BclI) on neonatal outcomes.
- To determine if GR gene variants modify the effects of prenatal steroid treatment in preterm infants.
- To analyze the association between GR polymorphisms and major neonatal morbidities.
Main Methods:
- A large cohort of 10,490 very-low-birth-weight (VLBW) preterm infants was studied across 49 German neonatal units.
- Genetic analysis focused on three GR polymorphisms: N363S (rs56149945), R23K (rs6190), and BclI (rs41423247).
- Neonatal outcomes were assessed, with logistic regression adjusting for gestational age, ventilation, and SGA status.
Main Results:
- The BclI genotype was associated with an increased risk of bronchopulmonary dysplasia (BPD) (OR 1.12, p=0.013).
- This increased BPD risk in BclI carriers was particularly evident in infants who received antenatal betamethasone (OR 1.16, p=0.003).
- No significant associations were found between N363S or R23K polymorphisms and neonatal outcomes.
Conclusions:
- The GR gene polymorphism BclI may increase the risk of BPD in VLBW preterm infants, especially with antenatal steroid exposure.
- The N363S and R23K GR gene polymorphisms did not demonstrate a significant impact on neonatal outcomes in this cohort.
- Further research is needed to fully elucidate the role of GR gene variants in neonatal care and response to prenatal therapies.
Background:
Induction of lung maturation by prenatal steroid treatment has become the standard of care for pregnant women at risk for preterm birth. In addition to the beneficial effects on lung maturation, prenatal steroids have been shown to reduce the incidence of neonatal death, necrotizing enterocolitis, sepsis, and intraventricular hemorrhage. However, little is known about the role of interindividual differences in corticoid sensitivity arising from polymorphisms in the glucocorticoid receptor (GR) gene.
Objectives:
To assess the impact of GR polymorphisms N363S (rs56149945), R23K (rs6190), and BclI (rs41423247) on neonatal outcome.
Methods:
The GR polymorphisms N363S, R23K, and BclI were examined in 10,490 very-low-birth-weight (VLBW) preterm infants from 49 German tertiary level neonatal units (German Neonatal Network, GNN) with respect to neonatal outcome.
Results:
Infants carrying the BclI genotype were at higher risk to develop bronchopulmonary dysplasia (BPD) (OR 1.12 per BclI allele, 95% CI: 1.02-1.23, p = 0.013) in a logistic regression model adjusted for gestational age, mechanical ventilation, and small for gestational age status. A similar relative risk was seen in the children (89.4%) who received antenatal betamethasone treatment (OR 1.16, 95% CI: 1.05-1.27, p = 0.003), whereas no such effect was detectable in infants without antenatal steroids. N363S and R23K did not show any stable association with neonatal outcome parameters.
Conclusion:
Except for a slightly higher risk of BPD in carriers of the GRBclI variant, the GR gene polymorphisms BclI, N363S, and R23K did not affect neonatal outcome parameters in this large multicenter cohort of VLBW preterm infants.
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