Journal
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume 22, Issue 12, Pages 1172-1177Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2010.10.003
Keywords
Hypomethylation; Neural tube defect; Tissue-specific methylation; Folate deficiency; Human fetus
Funding
- National Natural Science Foundation of China [30671156]
- National Basic Research Program of China [2007CB511903]
- Beijing Natural Science Foundation [5072014]
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This study compares the density and tissue-specific distribution of 5-methyl cytosine (5mC) in genomic DNA from human fetuses with or without neural tube defects (NTD) and examines whether low maternal serum folate is a possible correlate and/or risk factor for NTD. The results demonstrate significant hypomethylation of brain genomic DNA in NTD fetuses relative to controls (P<.01), as well as relative hypermethylation of skin and heart in NTD fetuses. In normal fetuses, the level of 5mC in liver genomic DNA decreased from fetal week 18 to 28 and increased over the same developmental period in kidney genomic DNA, but these trends were absent in genomic DNA from NTD fetuses. Mean maternal serum folate was significantly lower in NTD fetuses than in controls (P<.01), and maternal serum folate correlated with density of 5mC in genomic brain DNA from NTD fetuses (r=0.610). The results indicate that aberrant DNA methylation in NTD may be due to maternal folate deficiency and may be involved in the pathogenesis of NTD in humans. (C) 2011 Elsevier Inc. All rights reserved.
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