Steroid Pathway Genes and Neonatal Respiratory Distress After Betamethasone Use in Anticipated Preterm Birth.
OBJECTIVE
To test several key glucocorticoid genes that are enhanced in lung development for associations with respiratory distress syndrome (RDS) after antenatal corticosteroid use.


METHODS
A prospective cohort of women received betamethasone to accelerate fetal lung maturity for threatened preterm delivery. DNA was obtained from mothers and newborns. Neonatal RDS was the primary outcome. Genotyping for single-nucleotide polymorphisms (SNPs) in 68 glucocorticoid genes found to be differentially expressed during lung development was performed. Multivariable analysis tested for associations of SNPs in the candidate genes with RDS.


RESULTS
Genotypic results for 867 SNPs in 96 mothers and 73 babies were included. Thirty-nine (53.4%) babies developed RDS. Maternal SNPs in the centromeric protein E (CENPE), GLRX, CD9, and AURKA genes provided evidence of association with RDS (P < .01). In newborns, SNPs in COL4A3, BHLHE40, and SRGN provided evidence of association with RDS (P < .01).


CONCLUSIONS
Single-nucleotide polymorphisms in several glucocorticoid responsive genes suggest association with neonatal RDS after antenatal corticosteroid use.
Indiana University School of Medicine, Indianapolis, IN, USA dahaas@iupui.edu.
David M
DM
Haas
Indiana University School of Medicine, Indianapolis, IN, USA.
Dongbing
D
Lai
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
Sunita
S
Sharma
Indiana University School of Medicine, Indianapolis, IN, USA.
Jenny
J
Then
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
Alvin
A
Kho
Indiana University School of Medicine, Indianapolis, IN, USA.
David A
DA
Flockhart
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
Kelan
K
Tantisira
Indiana University School of Medicine, Indianapolis, IN, USA.
Tatiana
T
Foroud
D000328:Adult; D001623:Betamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D005938:Glucocorticoids / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics* / Q000517:prevention & control*; D011446:Prospective Studies; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy* / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D055815:Young Adult
D005938:Glucocorticoids; D001623:Betamethasone
antenatal corticosteroid; pharmacogenetics; pregnancy; preterm labor