title: DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans: results of a pilot randomized controlled trial.
abstract: Intrauterine exposures mediated by maternal diet may affect risk of cardiovascular disease, obesity, and type 2 diabetes. Recent evidence, primarily from animal studies and observational data in humans, suggests that the epigenome can be altered by maternal diet during the periconceptional period and that these programming events may underlie later disease risk. A randomized controlled trial of periconceptional micronutrient supplementation in The Gambia, where seasonal nutritional variations affect fetal growth and postnatal outcomes, provided a unique opportunity to test this hypothesis. Specifically, we targeted imprinted genes, which play important roles in allocation of maternal resources while being epigenetically regulated. DNA methylation at 12 differentially methylated regions (DMRs) was analyzed in cord blood samples from 58 offspring of women participating in a double-blind randomized-controlled trial of pre- and periconceptional micronutrient supplementation (including folate, zinc, and vitamins A, B, C, and D). We observed sex-specific effects of micronutrient supplementation, reducing methylation levels at two of the DMRs analyzed, IGF2R in girls and GTL2-2 in boys. This pilot study is the first to analyze DNA methylation in the context of a randomized controlled trial, and it provides suggestive evidence that periconceptional maternal nutrition alters offspring methylation at imprinted loci.
authors.affiliation: 2 Department of Paediatrics, Box 116, Level 8, Addenbrooke's Hospital, University of Cambridge, Hills Rd., Cambridge CB2 0QQ, UK.
authors.forename: Wendy N
authors.initials: WN
authors.lastname: Cooper
authors.forename: Batbayar
authors.initials: B
authors.lastname: Khulan
authors.forename: Stephen
authors.initials: S
authors.lastname: Owens
authors.forename: Cathy E
authors.initials: CE
authors.lastname: Elks
authors.forename: Veronica
authors.initials: V
authors.lastname: Seidel
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Prentice
authors.forename: Gusztav
authors.initials: G
authors.lastname: Belteki
authors.forename: Ken K
authors.initials: KK
authors.lastname: Ong
authors.forename: Nabeel A
authors.initials: NA
authors.lastname: Affara
authors.forename: Miguel
authors.initials: M
authors.lastname: Constância
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D000293:Adolescent; D000328:Adult; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D018977:Micronutrients / Q000008:administration & dosage*; D008875:Middle Aged; D010865:Pilot Projects; D010919:Placebos; D016742:Preconception Care; D055815:Young Adult
chemical_list: D018977:Micronutrients; D010919:Placebos