Higher serum homocysteine and lower thyroid hormone levels in pregnant women are associated with neural tube defects
Higher serum homocysteine and lower thyroid hormone levels in pregnant women are associated with neural tube defects
复制标题
DOI：
10.1016/j.jtemb.2021.126814
复制
发表时间：
2021-07-06
影响因子：
3.5
通讯作者：
Zhang, Ting
中科院分区：
文献类型：
--
作者：
Gu, Yan-Hong;Zhang, Qin;Zhang, Ting
背景：本研究检验了这样的假设：在中国 NTD 患病率较高的地区，孕妇同型半胱氨酸和甲状腺激素网络的母体代谢异常与神经管缺陷 (NTD) 相关。方法：2007年至2009年在山西省吕梁山区进行病例对照研究。这项研究包括 83 名胎儿患有 NTD 的孕妇（病例）和 90 名胎儿正常的孕妇（对照）。此外，还建立了细胞模型来说明流行病学发现。结果：使用多变量逻辑回归模型，总同型半胱氨酸 (tHcy) 较高且游离甲状腺素不足的母亲的胎儿患 NTD 的风险高出 3 倍（调整优势比 = 3.5；95% 置信区间 = 1.2-10.4；病例与对照）。此外，体外证明了 Hcy 和甲状腺激素代谢之间的生物相互作用。在 Hcy 处理的小鼠胚胎神经干 NE4C 细胞的代谢物同型半胱氨酸硫内酯中，与神经管闭合和甲状腺激素网络相关的基因（Bmp7、Ctnnb1、Notch 1、Gli2 和 Rxra）被证明受到 H3K79 同型半胱氨酸化的调节，从而增加了其表达水平。结论：母体血清高 tHcy 对发生 NTD 风险的影响取决于母体血清甲状腺素水平。同时，较高水平的tHcy还可能通过组蛋白的同型半胱氨酸化影响母体甲状腺激素的代谢和胚胎发生中神经管的闭合。
Background: This study tested the hypothesis that abnormal maternal metabolism of both homocysteine and thyroid hormone network in pregnant women is associated with neural tube defects (NTDs) in a part of China with high NTD prevalence. Methods: A case-control study was performed between 2007 and 2009 in Luliang Mountains, Shanxi Province. This study included 83 pregnant women who had fetuses with NTDs (cases) and 90 pregnant women with normal fetuses (controls). In addition, a cell model to illustrate the epidemiological findings was established. Results: Fetuses of mother who had both high total homocysteine (tHcy) and inadequate free thyroxine were 3 times more at risk of developing NTDs (adjusted odds ratio = 3.5; 95 % confidence interval = 1.2-10.4; cases vs. controls) using multivariate logistic regression models. Furthermore, biological interaction between metabolisms of Hcy and thyroid hormones was demonstrated in vitro. In homocysteine thiolactone of a metabolite of Hcytreated mouse embryonic neural stem NE4C cells, genes (Bmp7, Ctnnb1, Notch 1, Gli2, and Rxra) related to both neural tube closure and thyroid hormone network were shown to be regulated by H3K79 homocysteinylation, which increased their expression levels. Conclusions: The effect of maternal serum high tHcy on risk of developing NTDs is depended on maternal serum level of thyroxine. Meanwhile, a higher level of tHcy might also affect both maternal metabolism of thyroid hormone and neural tube closure in embryogenesis through homocysteinylation of histones.