title: Medical morbidities and DNA methylation of NR3C1 in preterm infants.
abstract: Although there are no accepted "normal" levels of circulating cortisol in preterm infants, critically ill preterm infants show lower cortisol levels than healthy preterm infants. The regulation of cortisol reactivity by epigenetic changes in glucocorticoid receptor gene (NR3C1) expression has been demonstrated. This study aims to examine the relationship between medical morbidities in preterm infants and DNA methylation of NR3C1.
  
  
  
  Pyrosequencing was used to determine DNA methylation in CpG sites 1-4 of promoter region 1F of NR3C1. Cluster analysis placed 67 preterm infants born <1,500 g into groups based on medical morbidities. The DNA methylation pattern was compared across groups.
  
  
  
  Cluster analysis identified a high medical risk cluster and a low medical risk cluster. A Mann-Whitney U-test showed lower methylation at CpG1 for infants in the high-risk group (M = 0.336, SE = 0.084) than infants in the low-risk group (M = 0.617, SE = 0.109, P = 0.032). The false discovery rate was low (q = 0.025). Cohen's D effect size was moderate (0.525).
  
  
  
  Decreased DNA methylation of CpG1 of NR3C1 in high-risk infants may allow for increased binding of transcription factors involved in the stress response, repair and regulation of NR3C1. This may ensure healthy growth in high-risk preterm infants over increasing cortisol levels.
authors.affiliation: Department of Neuroscience, Brown University, Providence, Rhode Island.|Warren Alpert Medical School of Brown University, Center for the Study of Children at Risk, Providence, Rhode Island.
authors.forename: James
authors.initials: J
authors.lastname: Giarraputo
authors.affiliation: Warren Alpert Medical School of Brown University, Center for the Study of Children at Risk, Providence, Rhode Island.|Department of Sociology, Brown University, Providence, Rhode Island.
authors.forename: Jordan
authors.initials: J
authors.lastname: DeLoach
authors.affiliation: Warren Alpert Medical School of Brown University, Departments of Pediatrics, Providence, Rhode Island.|Department of Pediatrics, Women and Infants Hospital of Rhode Island, Providence, Rhode Island.
authors.forename: James
authors.initials: J
authors.lastname: Padbury
authors.affiliation: Warren Alpert Medical School of Brown University, Departments of Pediatrics, Providence, Rhode Island.|Department of Pediatrics, Women and Infants Hospital of Rhode Island, Providence, Rhode Island.
authors.forename: Alper
authors.initials: A
authors.lastname: Uzun
authors.affiliation: Department of Pharmacology and Toxicology and Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
authors.forename: Carmen
authors.initials: C
authors.lastname: Marsit
authors.affiliation: Warren Alpert Medical School of Brown University, Center for the Study of Children at Risk, Providence, Rhode Island.|Warren Alpert Medical School of Brown University, Departments of Pediatrics, Providence, Rhode Island.|Department of Pediatrics, Women and Infants Hospital of Rhode Island, Providence, Rhode Island.
authors.forename: Katheleen
authors.initials: K
authors.lastname: Hawes
authors.affiliation: Warren Alpert Medical School of Brown University, Center for the Study of Children at Risk, Providence, Rhode Island.|Warren Alpert Medical School of Brown University, Departments of Pediatrics, Providence, Rhode Island.|Department of Pediatrics, Women and Infants Hospital of Rhode Island, Providence, Rhode Island.|Warren Alpert Medical School of Brown University, Departments of Psychiatry and Human Behavior, Providence, Rhode Island.
authors.forename: Barry
authors.initials: B
authors.lastname: Lester
mesh_terms: D018899:CpG Islands; D016638:Critical Illness; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D018869:Heat-Shock Response / Q000235:genetics; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D008297:Male; D009017:Morbidity; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012307:Risk Factors; D013312:Stress, Physiological; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D006854:Hydrocortisone