title: Leptin gene epigenetic adaptation to impaired glucose metabolism during pregnancy.
abstract: OBJECTIVE
  To verify whether the leptin gene epigenetic (DNA methylation) profile is altered in the offspring of mothers with gestational impaired glucose tolerance (IGT).
  
  
  METHODS
  Placental tissues and maternal and cord blood samples were obtained from 48 women at term including 23 subjects with gestational IGT. Leptin DNA methylation, gene expression levels, and circulating concentration were measured using the Sequenom EpiTYPER system, quantitative real-time RT-PCR, and enzyme-linked immunosorbent assay, respectively. IGT was assessed after a 75-g oral glucose tolerance test (OGTT) at 24-28 weeks of gestation.
  
  
  RESULTS
  We have shown that placental leptin gene DNA methylation levels were correlated with glucose levels (2-h post-OGTT) in women with IGT (fetal side: ρ=-0.44, P≤0.05; maternal side: ρ=0.53, P≤0.01) and with decreased leptin gene expression (n=48; ρ≥-0.30, P≤0.05) in the whole cohort. Placental leptin mRNA levels accounted for 16% of the variance in maternal circulating leptin concentration (P<0.05).
  
  
  CONCLUSIONS
  IGT during pregnancy was associated with leptin gene DNA methylation adaptations with potential functional impacts. These epigenetic changes provide novel mechanisms that could contribute to explaining the detrimental health effects associated with fetal programming, such as long-term increased risk of developing obesity and type 2 diabetes.
authors: Department of Medicine, Université de Montréal, Montréal, Quebec, Canada. luigi.bouchard@recherche-caurc.org
authors: Luigi
authors: L
authors: Bouchard
authors: Stéphanie
authors: S
authors: Thibault
authors: Simon-Pierre
authors: SP
authors: Guay
authors: Marta
authors: M
authors: Santure
authors: Alexandre
authors: A
authors: Monpetit
authors: Julie
authors: J
authors: St-Pierre
authors: Patrice
authors: P
authors: Perron
authors: Diane
authors: D
authors: Brisson
mesh_terms: D000328:Adult; D019175:DNA Methylation; D005260:Female; D018149:Glucose Intolerance / Q000235:genetics*; D005951:Glucose Tolerance Test; D006801:Humans; D020738:Leptin / Q000235:genetics*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020738:Leptin