Tissue-specific distribution of aberrant DNA methylation associated with maternal low-folate status in human neural tube defects

被引：83

作者：

Chang, Huibo ^{[1
]}

Zhang, Ting ^{[2
]}

Zhang, Zhiping ^{[1
]}

Bao, Rui ^{[1
]}

Fu, Chengbo ^{[3
]}

Wang, Zhigang ^{[1
]}

Bao, Yihua ^{[2
]}

Li, Yuanyuan ^{[1
]}

Wu, Lihua ^{[2
]}

Zheng, Xiaoying ^{[4
]}

Wu, Jianxin ^{[1
,3
]}

机构：

[1] Capital Inst Pediat, Dept Biochem, Beijing 100020, Peoples R China

[2] Capital Inst Pediat, Dept Mol Immunol, Beijing 100020, Peoples R China

[3] Peking Union Med Coll, Beijing 100730, Peoples R China

[4] Peking Univ, World Hlth Org Collaborating Ctr Res Reprod Hlth, Inst Populat Res, Beijing 100871, Peoples R China

来源：

JOURNAL OF NUTRITIONAL BIOCHEMISTRY | 2011年 / 22卷 / 12期

基金：

北京市自然科学基金; 中国国家自然科学基金;

关键词：

Hypomethylation; Neural tube defect; Tissue-specific methylation; Folate deficiency; Human fetus; SHANXI PROVINCE; HIGH PREVALENCE; FOLIC-ACID; DEFICIENCY; CELL; HYPOMETHYLATION; INHIBITION; METHIONINE; EXPRESSION; PATTERNS;

D O I：

10.1016/j.jnutbio.2010.10.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1172 / 1177

页数：6

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