title: Tissue-specific distribution of aberrant DNA methylation associated with maternal low-folate status in human neural tube defects.
abstract: 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.
authors.affiliation: Department of Biochemistry, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Huibo
authors.initials: H
authors.lastname: Chang
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Bao
authors.forename: Chengbo
authors.initials: C
authors.lastname: Fu
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.forename: Yihua
authors.initials: Y
authors.lastname: Bao
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.forename: Lihua
authors.initials: L
authors.lastname: Wu
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zheng
authors.forename: Jianxin
authors.initials: J
authors.lastname: Wu
mesh_terms: D019175:DNA Methylation; D005260:Female; D005333:Fetus; D005492:Folic Acid / Q000097:blood*; D005494:Folic Acid Deficiency / Q000235:genetics / Q000378:metabolism*; D015894:Genome, Human; D006801:Humans; D054259:Neural Tube / Q000473:pathology; D009436:Neural Tube Defects / Q000235:genetics*; D009928:Organ Specificity; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors
chemical_list: D005492:Folic Acid