title: The impact of drug metabolizing enzyme polymorphisms on outcomes after antenatal corticosteroid use.
abstract: OBJECTIVE
  To determine the impact of maternal and fetal single nucleotide polymorphisms in key betamethasone pathways on neonatal outcomes.
  
  
  METHODS
  DNA was obtained from women given betamethasone and their infants. Samples were genotyped for 73 exploratory drug metabolism and glucocorticoid pathway single nucleotide polymorphisms. Clinical variables and neonatal outcomes were obtained. Logistic regression analysis using relevant clinical variables and genotypes to model for associations with neonatal respiratory distress syndrome was performed.
  
  
  RESULTS
  One hundred nine women delivering 117 infants were analyzed. Sixty-four infants (49%) developed respiratory distress syndrome. Multivariable analysis revealed that respiratory distress syndrome was associated with maternal single nucleotide polymorphisms in CYP3A5 (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.16-2.30) and the glucocorticoid resistance (OR, 0.28; 95% CI, 0.08-0.95) and fetal single nucleotide polymorphisms in ADCY9 (OR, 0.17; 95% CI, 0.03-0.80) and CYP3A7*1E (rs28451617; OR, 23.68; 95% CI, 1.33-420.6).
  
  
  CONCLUSIONS
  Maternal and fetal genotypes are independently associated with neonatal respiratory distress syndrome after treatment with betamethasone for preterm labor.
authors.affiliation: The Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Haas
authors.forename: Amalia S
authors.initials: AS
authors.lastname: Lehmann
authors.forename: Todd
authors.initials: T
authors.lastname: Skaar
authors.forename: Santosh
authors.initials: S
authors.lastname: Philips
authors.forename: Catherine L
authors.initials: CL
authors.lastname: McCormick
authors.forename: Kyle
authors.initials: K
authors.lastname: Beagle
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hebbring
authors.forename: Jessica
authors.initials: J
authors.lastname: Dantzer
authors.forename: Lang
authors.initials: L
authors.lastname: Li
authors.forename: Jeesun
authors.initials: J
authors.lastname: Jung
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000262:Adenylyl Cyclases / Q000235:genetics; D000328:Adult; D015239:Arylsulfotransferase / Q000235:genetics; D001623:Betamethasone / Q000378:metabolism* / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D060005:Genotyping Techniques; D005938:Glucocorticoids / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D016015:Logistic Models; D015999:Multivariate Analysis; D007752:Obstetric Labor, Premature; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012372:ROC Curve; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics; D012127:Respiratory Distress Syndrome, Newborn / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D016896:Treatment Outcome; D000099052:CRF Receptor, Type 1
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005819:Genetic Markers; D005938:Glucocorticoids; C497713:NR3C1 protein, human; D018019:Receptors, Corticotropin-Releasing Hormone; D011965:Receptors, Glucocorticoid; D000099052:CRF Receptor, Type 1; D001623:Betamethasone; D051544:Cytochrome P-450 CYP3A; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; D000262:Adenylyl Cyclases; C413923:adenylate cyclase 9