Tissue-specific distribution of aberrant DNA methylation associated with maternal low-folate status in human neural tube defects |
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Authors: | Chang Huibo Zhang Ting Zhang Zhiping Bao Rui Fu Chengbo Wang Zhigang Bao Yihua Li Yuanyuan Wu Lihua Zheng Xiaoying Wu Jianxin |
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Institution: | a Department of Biochemistry, Capital Institute of Pediatrics, Beijing 100020, Chinab Department of Molecular Immunology, Capital Institute of Pediatrics, Beijing 100020, Chinac Peking Union Medical College, Beijing 100730, Chinad World Health Organization Collaborating Center for Research in Reproductive Health and Population Science, Institute of Population Research, Peking University, Beijing 100871, China |
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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. |
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Keywords: | Hypomethylation Neural tube defect Tissue-specific methylation Folate deficiency Human fetus |
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