title: Placental and Cord Blood Methylation of Genes Involved in Energy Homeostasis: Association With Fetal Growth and Neonatal Body Composition.
abstract: Low weight at birth is associated with subsequent susceptibility to diabetes. Epigenetic modulation is among the mechanisms potentially mediating this association. We performed a genome-wide DNA methylation analysis in placentas from term infants born appropriate-for-gestational-age (AGA) or small-for-gestational-age (SGA) to identify new genes related to fetal growth and neonatal body composition. Candidate genes were validated by bisulfite pyrosequencing (30 AGA, 21 SGA) and also analyzed in cord blood. Gene expression analyses were performed by RT-PCR. Neonatal body composition was assessed by dual X-ray absorptiometry at age 2 weeks. TheATG2B,NKX6.1,andSLC13A5genes (respectively related to autophagy, β-cell development and function, and lipid metabolism) were hypermethylated in placenta and cord blood from SGA newborns, whereasGPR120(related to free fatty acid regulation) was hypomethylated in placenta and hypermethylated in cord blood. Gene expression levels were opposite to methylation status, and both correlated with birth weight, circulating IGF-I, and total and abdominal fat at age 2 weeks. In conclusion, alterations in methylation and expression of genes involved in the regulation of energy homeostasis were found to relate to fetal growth and neonatal body composition and thus may be among the early mechanisms modulating later susceptibility to diabetes.
authors.affiliation: Institut Pediàtric, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.|CIBERDEM, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Díaz
authors.affiliation: Institut Pediàtric, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.|CIBERDEM, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: García
authors.affiliation: Institut Pediàtric, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.|CIBERDEM, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Sebastiani
authors.affiliation: Department of Development and Regeneration, University of Leuven, Leuven, Belgium.
authors.forename: Francis
authors.initials: F
authors.lastname: de Zegher
authors.affiliation: Department of Pediatrics, Dr. Josep Trueta Hospital, Girona, Spain.|Girona Institute for Biomedical Research, Girona, Spain.
authors.forename: Abel
authors.initials: A
authors.lastname: López-Bermejo
authors.affiliation: Institut Pediàtric, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain libanez@hsjdbcn.org.|CIBERDEM, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ibáñez
mesh_terms: D050153:Abdominal Fat; D000273:Adipose Tissue; D000328:Adult; D000071183:Autophagy-Related Proteins / Q000235:genetics; D001724:Birth Weight / Q000235:genetics; D001823:Body Composition / Q000235:genetics*; D001827:Body Height / Q000235:genetics; D001835:Body Weight; D015519:Bone Density; D016022:Case-Control Studies; D019175:DNA Methylation / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D047109:Fetal Development / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D006706:Homeostasis; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008297:Male; D009929:Organ Size; D010920:Placenta / Q000033:anatomy & histology / Q000378:metabolism*; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D027981:Symporters / Q000235:genetics; D047929:Term Birth; D059467:Transcriptome; D033921:Vesicular Transport Proteins / Q000235:genetics
chemical_list: C572313:ATG2B protein, human; D000071183:Autophagy-Related Proteins; C519853:FFAR4 protein, human; D018398:Homeodomain Proteins; C105201:NKX6-1 protein, human; D043562:Receptors, G-Protein-Coupled; C470492:SLC13A5 protein, human; D027981:Symporters; D033921:Vesicular Transport Proteins