title: Quantitative, high-resolution epigenetic profiling of CpG loci identifies associations with cord blood plasma homocysteine and birth weight in humans.
abstract: Supplementation with folic acid during pregnancy is known to reduce the risk of neural tube defects and low birth weight. It is thought that folate and other one-carbon intermediates might secure these clinical effects via DNA methylation. We examined the effects of folate on the human methylome using quantitative interrogation of 27,578 CpG loci associated with 14,496 genes at single-nucleotide resolution across 12 fetal cord blood samples. Consistent with previous studies, the majority of CpG dinucleotides located within CpG islands exhibited hypo-methylation while those outside CpG islands showed mid-high methylation. However, for the first time in human samples, unbiased analysis of methylation across samples revealed a significant correlation of methylation patterns with plasma homocysteine, LINE-1 methylation and birth weight centile. Additionally, CpG methylation significantly correlated with either birth weight or LINE-1 methylation were predominantly located in CpG islands. These data indicate that levels of folate-associated intermediates in cord blood reflect their influence and consequences for the fetal epigenome and potentially on pregnancy outcome. In these cases, their influence might be exerted during late gestation or reflect those present during the peri-conceptual period.
authors.affiliation: Institute of Science and Technology in Medicine, Keele University School of Medicine, University Hospital of North Staffordshire; Stoke-on-Trent, Staffordshire, UK.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Fryer
authors.forename: Richard D
authors.initials: RD
authors.lastname: Emes
authors.forename: Khaled M K
authors.initials: KM
authors.lastname: Ismail
authors.forename: Kim E
authors.initials: KE
authors.lastname: Haworth
authors.forename: Charles
authors.initials: C
authors.lastname: Mein
authors.forename: William D
authors.initials: WD
authors.lastname: Carroll
authors.forename: William E
authors.initials: WE
authors.lastname: Farrell
mesh_terms: D001724:Birth Weight / Q000187:drug effects / Q000502:physiology*; D018899:CpG Islands / Q000502:physiology; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005492:Folic Acid / Q000008:administration & dosage; D020869:Gene Expression Profiling; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000502:physiology*; D008297:Male; D009436:Neural Tube Defects / Q000097:blood / Q000235:genetics / Q000517:prevention & control; D011247:Pregnancy / Q000097:blood* / Q000187:drug effects / Q000235:genetics; D014803:Vitamin B Complex / Q000008:administration & dosage
chemical_list: D006710:Homocysteine; D014803:Vitamin B Complex; D005492:Folic Acid