title: Tissue-specific Leptin promoter DNA methylation is associated with maternal and infant perinatal factors.
abstract: Leptin a regulator of body weight is involved in reproductive and developmental functions. Leptin promoter DNA methylation (LEP) regulates gene expression in a tissue-specific manner and has been linked to adverse pregnancy outcomes. In non-pathologic human pregnancies, we assessed LEP methylation, genotyped the single nucleotide polymorphism (SNP) rs2167270 in placental (n=81), maternal and cord blood samples (n=60), and examined the association between methylation, genotype, and perinatal factors. Maternal blood LEP methylation was lower in pre-pregnancy obese women (P=0.01). Cord blood LEP methylation was higher in small for gestational age (SGA) (P=4.6×10(-3)) and A/A genotype (P=1.6×10(-4)), lower (-1.47, P=0.03) in infants born to pre-pregnancy obese mothers and correlated (P=0.01) with maternal blood LEP. Gender was associated with placental LEP methylation (P=0.05). These results suggest that LEP epigenetic control may be influenced by perinatal factors including: maternal obesity, infant growth, genotype and gender in a tissue-specific manner and may have multigenerational implications.
authors.affiliation: Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, 7650 Remsen, Hanover, NH 03755, USA. Electronic address: corina.lesseur.perez.GR@dartmouth.edu.
authors.forename: Corina
authors.initials: C
authors.lastname: Lesseur
authors.forename: David A
authors.initials: DA
authors.lastname: Armstrong
authors.forename: Alison G
authors.initials: AG
authors.lastname: Paquette
authors.forename: Devin C
authors.initials: DC
authors.lastname: Koestler
authors.forename: James F
authors.initials: JF
authors.lastname: Padbury
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
mesh_terms: D000328:Adult; D001724:Birth Weight; D015992:Body Mass Index; D019175:DNA Methylation; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D020738:Leptin / Q000097:blood / Q000235:genetics*; D008297:Male; D009928:Organ Specificity; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011401:Promoter Regions, Genetic
chemical_list: D020738:Leptin
keywords: AGA; C/EBP α; CAAT-enhancer binding protein alpha; DNA methylation; DOHaD; Epigenetics; GWG; LEP; LGA; Leptin; Leptin promoter DNA methylation; Maternal obesity; Pregnancy; SD; SGA; SNP; SP1; Std.Error; adequate for gestational age; developmental origins of adult health and disease; gestational weight gain; large for gestational age; large for gestational age, BMI, body mass index; rs2167270; single nucleotide polymorphism; small for gestational age; specificity protein; standard deviation; standard error
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