title: Maternal intake of methyl-group donors affects DNA methylation of metabolic genes in infants.
abstract: Maternal nutrition during pregnancy and infant nutrition in the early postnatal period (lactation) are critically involved in the development and health of the newborn infant. The Maternal Nutrition and Offspring's Epigenome (MANOE) study was set up to assess the effect of maternal methyl-group donor intake (choline, betaine, folate, methionine) on infant DNA methylation. Maternal intake of dietary methyl-group donors was assessed using a food-frequency questionnaire (FFQ). Before and during pregnancy, we evaluated maternal methyl-group donor intake through diet and supplementation (folic acid) in relation to gene-specific (IGF2DMR,DNMT1,LEP,RXRA) buccal epithelial cell DNA methylation in 6 months old infants (n= 114) via pyrosequencing. In the early postnatal period, we determined the effect of maternal choline intake during lactation (in mothers who breast-fed for at least 3 months) on gene-specific buccal DNA methylation (n= 65).
  
  
  
  Maternal dietary and supplemental intake of methyl-group donors (folate, betaine, folic acid), only in the periconception period, was associated with buccal cell DNA methylation in genes related to growth (IGF2DMR), metabolism (RXRA), and appetite control (LEP). A negative association was found between maternal folate and folic acid intake before pregnancy and infantLEP(slope = -1.233, 95% CI -2.342; -0.125,p= 0.0298) andIGF2DMR methylation (slope = -0.706, 95% CI -1.242; -0.107,p= 0.0101), respectively. Positive associations were observed for maternal betaine (slope = 0.875, 95% CI 0.118; 1.633,p= 0.0241) and folate (slope = 0.685, 95% CI 0.245; 1.125,p= 0.0027) intake before pregnancy andRXRAmethylation. BuccalDNMT1methylation in the infant was negatively associated with maternal methyl-group donor intake in the first and second trimester of pregnancy and negatively in the third trimester. We found no clear association between maternal choline intake during lactation and buccal infant DNA methylation.
  
  
  
  This study suggests that maternal dietary and supplemental intake of methyl-group donors, especially in the periconception period, can influence infant's buccal DNA methylation in genes related to metabolism, growth, appetite regulation, and maintenance of DNA methylation reactions.
authors.affiliation: Department of Public Health and Primary Care, Environment and Health, KU Leuven - University of Leuven, Kapucijnenvoer 35 blok D box 7001, 3000 Leuven, Belgium.|Flemish Institute of Technological Research (VITO), Unit Environmental Risk and Health, Boeretang 200, 2400 Mol, Belgium.
authors.forename: Sara
authors.initials: S
authors.lastname: Pauwels
authors.affiliation: Department of Public Health and Primary Care, Environment and Health, KU Leuven - University of Leuven, Kapucijnenvoer 35 blok D box 7001, 3000 Leuven, Belgium.
authors.forename: Manosij
authors.initials: M
authors.lastname: Ghosh
authors.affiliation: Department of Public Health and Primary Care, Environment and Health, KU Leuven - University of Leuven, Kapucijnenvoer 35 blok D box 7001, 3000 Leuven, Belgium.
authors.forename: Radu Corneliu
authors.initials: RC
authors.lastname: Duca
authors.affiliation: Department of Imaging & Pathology, KU Leuven - University of Leuven, 3000 Leuven, Belgium.|University Hospitals Leuven; Department of Forensic Medicine; Laboratory of Forensic Genetics and Molecular Archeology, KU Leuven - University of Leuven, 3000 Leuven, Belgium.
authors.forename: Bram
authors.initials: B
authors.lastname: Bekaert
authors.affiliation: Center for Molecular and Vascular Biology, KU Leuven - University of Leuven, UZ Herestraat 49 - box 911, 3000 Leuven, Belgium.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Freson
authors.affiliation: International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon, CEDEX 08, France.
authors.forename: Inge
authors.initials: I
authors.lastname: Huybrechts
authors.affiliation: Flemish Institute of Technological Research (VITO), Unit Environmental Risk and Health, Boeretang 200, 2400 Mol, Belgium.|Faculty of Sciences, Hasselt University, 3590 Diepenbeek, Belgium.
authors.forename: Sabine A S
authors.initials: SAS
authors.lastname: Langie
authors.affiliation: Flemish Institute of Technological Research (VITO), Unit Environmental Risk and Health, Boeretang 200, 2400 Mol, Belgium.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Koppen
authors.affiliation: Department of Development and Regeneration, KU Leuven - University of Leuven, 3000 Leuven, Belgium.|Department of Obstetrics and Gynecology, University Hospitals of Leuven, 3000 Leuven, Belgium.
authors.forename: Roland
authors.initials: R
authors.lastname: Devlieger
authors.affiliation: Department of Public Health and Primary Care, Environment and Health, KU Leuven - University of Leuven, Kapucijnenvoer 35 blok D box 7001, 3000 Leuven, Belgium.|IDEWE, External Service for Prevention and Protection at Work, Interleuvenlaan 58, 3001 Heverlee, Belgium.
authors.forename: Lode
authors.initials: L
authors.lastname: Godderis
mesh_terms: D001622:Betaine / Q000008:administration & dosage*; D002794:Choline / Q000008:administration & dosage*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects*; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D007223:Infant; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D020738:Leptin / Q000235:genetics; D039382:Maternal Nutritional Physiological Phenomena; D009749:Nutrition Surveys; D011247:Pregnancy; D047490:Retinoid X Receptor alpha / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: C035170:IGF2 protein, human; D020738:Leptin; D047490:Retinoid X Receptor alpha; D001622:Betaine; D007335:Insulin-Like Growth Factor II; D005492:Folic Acid; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; D002794:Choline
keywords: DNA methylation; DNMT1; IGF2 DMR; LEP; Lactation; Methyl-group donors; Pregnancy; RXRA