David M Haas1, Dongbing Lai2, Sunita Sharma3, Jenny Then2, Alvin Kho3, David A Flockhart2, Kelan Tantisira3, Tatiana Foroud2. 1. Indiana University School of Medicine, Indianapolis, IN, USA dahaas@iupui.edu. 2. Indiana University School of Medicine, Indianapolis, IN, USA. 3. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
Abstract
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). CONCLUSION: Single-nucleotide polymorphisms in several glucocorticoid responsive genes suggest association with neonatal RDS after antenatal corticosteroid use.
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). CONCLUSION: Single-nucleotide polymorphisms in several glucocorticoid responsive genes suggest association with neonatal RDS after antenatal corticosteroid use.
Authors: S M Dolan; M V Hollegaard; M Merialdi; A P Betran; T Allen; C Abelow; J Nace; B K Lin; M J Khoury; J P A Ioannidis; S Bagade; X Zheng; R A Dubin; L Bertram; D R Velez Edwards; R Menon Journal: Public Health Genomics Date: 2010-05-20 Impact factor: 2.000
Authors: Alkes L Price; Nick J Patterson; Robert M Plenge; Michael E Weinblatt; Nancy A Shadick; David Reich Journal: Nat Genet Date: 2006-07-23 Impact factor: 38.330
Authors: Sunita Sharma; Kelan Tantisira; Vincent Carey; Amy J Murphy; Jessica Lasky-Su; Juan C Celedón; Ross Lazarus; Barbara Klanderman; Angela Rogers; Manuel Soto-Quirós; Lydiana Avila; Thomas Mariani; Roger Gaedigk; Stephen Leeder; John Torday; David Warburton; Benjamin Raby; Scott T Weiss Journal: Am J Respir Crit Care Med Date: 2009-11-19 Impact factor: 21.405
Authors: T Foroud; S Ichikawa; D Koller; D Lai; L Curry; X Xuei; H J Edenberg; S Hui; M Peacock; M J Econs Journal: Osteoporos Int Date: 2007-10-02 Impact factor: 4.507
Authors: Ritva Haataja; Minna K Karjalainen; Aino Luukkonen; Kari Teramo; Hilkka Puttonen; Marja Ojaniemi; Teppo Varilo; Bimal P Chaudhari; Jevon Plunkett; Jeffrey C Murray; Steven A McCarroll; Leena Peltonen; Louis J Muglia; Aarno Palotie; Mikko Hallman Journal: PLoS Genet Date: 2011-02-03 Impact factor: 5.917