title: Maternal obesity and gestational diabetes are associated with placental leptin DNA methylation.
abstract: OBJECTIVE
  In this study, we aimed to investigate relationships between maternal prepregnancy obesity and gestational diabetes mellitus and placental leptin DNA methylation.
  
  
  METHODS
  This study comprises data on 535 mother-infant dyads enrolled in the Rhode Island Child Health Study, a prospective cohort study of healthy term pregnancies. Prepregnancy body mass index was calculated from self-reported anthropometric measures and gestational diabetes mellitus diagnoses gathered from inpatient medical records. DNA methylation of the leptin promoter region was assessed in placental tissue collected at birth using quantitative bisulfite pyrosequencing.
  
  
  RESULTS
  In a multivariable regression analysis adjusted for confounders, infants exposed to gestational diabetes mellitus had higher placental leptin methylation (β = 1.89, P = .04), as did those demonstrating prepregnancy obesity (β = 1.17, P = .06). Using a structural equations model, we observed that gestational diabetes mellitus is a mediator of the effects of prepregnancy obesity on placental leptin DNA methylation (β = 0.81, 95% confidence interval, 0.27-2.71).
  
  
  CONCLUSIONS
  Our results suggest that the maternal metabolic status before and during pregnancy can alter placental DNA methylation profile at birth and potentially contribute to metabolic programming of obesity and related conditions.
authors: Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, NH.
authors: Corina
authors: C
authors: Lesseur
authors: Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, NH.
authors: David A
authors: DA
authors: Armstrong
authors: Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, NH.
authors: Alison G
authors: AG
authors: Paquette
authors: Section of Biostatistics and Epidemiology, Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Lebanon, NH.
authors: Zhigang
authors: Z
authors: Li
authors: Department of Pediatrics, Women and Infants Hospital of Rhode Island, Brown University, Providence, RI.
authors: James F
authors: JF
authors: Padbury
authors: Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, NH; Section of Biostatistics and Epidemiology, Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Lebanon, NH. Electronic address: Carmen.J.Marsit@dartmouth.edu.
authors: Carmen J
authors: CJ
authors: Marsit
mesh_terms: D000328:Adult; D015992:Body Mass Index; D015331:Cohort Studies; D019175:DNA Methylation / Q000235:genetics*; D016640:Diabetes, Gestational / Q000235:genetics*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D020738:Leptin / Q000235:genetics*; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D009765:Obesity / Q000235:genetics*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D020738:Leptin
keywords: DNA methylation; gestational diabetes mellitus; leptin; maternal obesity; placenta