Document Detail


Quantitative, high-resolution epigenetic profiling of CpG loci identifies associations with cord blood plasma homocysteine and birth weight in humans.
MedLine Citation:
PMID:  20864804     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Anthony A Fryer; Richard D Emes; Khaled M K Ismail; Kim E Haworth; Charles Mein; William D Carroll; William E Farrell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-01-01
Journal Detail:
Title:  Epigenetics : official journal of the DNA Methylation Society     Volume:  6     ISSN:  1559-2308     ISO Abbreviation:  Epigenetics     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-26     Completed Date:  2011-04-25     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  101265293     Medline TA:  Epigenetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  86-94     Citation Subset:  IM    
Affiliation:
Institute of Science and Technology in Medicine, Keele University School of Medicine, University Hospital of North Staffordshire; Stoke-on-Trent, Staffordshire, UK.
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MeSH Terms
Descriptor/Qualifier:
Birth Weight / drug effects,  physiology*
CpG Islands / physiology
Epigenesis, Genetic / drug effects,  physiology*
Female
Fetal Blood / metabolism*
Folic Acid / administration & dosage
Gene Expression Profiling
Homocysteine / blood*
Humans
Long Interspersed Nucleotide Elements / physiology*
Male
Neural Tube Defects / blood,  genetics,  prevention & control
Pregnancy / blood*,  drug effects,  genetics
Vitamin B Complex / administration & dosage
Chemical
Reg. No./Substance:
12001-76-2/Vitamin B Complex; 454-28-4/Homocysteine; 59-30-3/Folic Acid
Comments/Corrections

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