Global DNA Hypomethylation Is Associated with NTD-Affected Pregnancy: A Case-Control Study

Global DNA Hypomethylation Is Associated with NTD-Affected Pregnancy: A Case-Control Study
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DOI:
10.1002/bdra.20670
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发表时间:
2010-07-01
影响因子:
--
通讯作者:
Zhang, Ting
Zhang, Ting
中科院分区:
医学4区
文献类型:
--
作者:
Chen, Xiaoli;Guo, Jin;Zhang, Ting

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背景:神经管缺陷是严重的,常见的出生缺陷,导致神经管关闭失败。它们被认为是一种多因素疾病,我们对因果机制的了解仍然有限。我们假设异常DNA甲基化发生在NTD影响的胎儿。分析NTDs的复杂性与NTDs的危险因素MTHFR基因型和发热之间的相关性。方法:采用以医院为基础的病例对照研究。完成流行病学资料、病理诊断和亚甲基四氢叶酸还原酶(MTHFR)基因型分析。阵列比较基因组杂交用于排除细胞遗传学异常。确定脑和皮肤组织的总体DNA甲基化状态。结果:收集了65例NTD影响的胎儿和65例正常对照,其孕周和母亲年龄相匹配。在脑组织中,与对照组相比,病例组的总体DNA甲基化水平显著降低(4.12 vs. 4.99%; p < 0.001)。DNA低甲基化(
BACKGROUND: Neural tube defects are severe, common birth defects that result from failure of neural tube closure. They are considered to be a multifactorial disorder, and our knowledge of causal mechanisms remains limited. We hypothesized that abnormal DNA methylation occurs in NTD-affected fetuses. The correlations of global DNA methylation levels with complexity of NTDs and known risk factors of NTIDs, MTHFR genotype and fever, were analyzed. METHODS: A hospital-based case-control study was performed. Epidemiologic data, pathologic diagnosis, and methylenetetrahydrofolate reductase (MTHFR) genotype analysis were completed. Array comparative genomic hybridization was used to exclude cytogenetic abnormalities. Global DNA methylation statuses were determined for both brain and skin tissue. RESULTS: Sixty-five NTD-affected fetuses and 65 normal controls matched for gestational and maternal ages were collected. In brain tissue, global DNA methylation levels were significantly decreased in cases compared with controls (4.12 vs. 4.99%; p < 0.001.). DNA hypomethylation (