全表观基因组DNA甲基化特征在铜与SGA关联中的中介作用

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology Pub Date : 2025-06-18 DOI:10.1016/j.jtemb.2025.127688

Weiwei Wu , Mengru Wang , Shan Li , Bole Zhang , Weixuan Hu , Yulin Li , Yongliang Feng , Yawei Zhang , Suping Wang

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引用次数: 0

摘要

背景微量元素Cu与胎龄儿小的风险相关，但其潜在机制尚不清楚。本研究旨在从DNA甲基化的角度探讨Cu诱导SGA的可能机制。方法对出生时小胎龄婴儿（SGA, n = 35）和适合胎龄婴儿（AGA, n = 61）的脐带血进行表观基因组DNA甲基化分析，探索与SGA相关的表观基因组DNA甲基化位点。采用电感耦合等离子体质谱法（ICP-MS）检测其脐带血铜水平。采用多元线性回归模型探讨Cu对sga相关DNA甲基化位点的影响，并进一步应用中介分析探索DNA甲基化的潜在中介因素。错误发现率（FDR）用于多重比较。结果与AGA（452 ng/mL）相比，SGA患儿脐带血Cu浓度（532 ng/mL）较高（P <； 0.05）。通过SGA的表观基因组DNA甲基化关联分析，鉴定出7个cu相关的CpG位点。其中，FLT3（cg10763141）甲基化水平在高铜暴露水平与SGA的关联中具有显著中介作用（P = 0.024）。中介分析显示，中介比例为44.7 %。结论与之前的研究结果一致，我们发现Cu与SGA的风险相关，并且在SGA的表观基因组DNA甲基化关联研究中观察到7个与Cu显著相关的差异甲基化位点。FLT3（cg10763141）介导Cu和SGA之间的相关性。铜可能通过改变某些基因（特别是FLT3）的DNA甲基化而增加SGA的风险。我们的研究为SGA的机制提供了新的线索。

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Mediating role of whole epigenome DNA methylation signatures in the association between copper and SGA

Background

Trace element Cu is associated with the risk of small for gestational age infants, but its underlying mechanism is still unclear. This study aims to explore the possible mechanism of Cu induced SGA from the perspective of DNA methylation.

Methods

We performed epigenome-wide DNA methylation analysis of umbilical cord blood from small for gestational age infants (SGA, n = 35) and appropriate for gestational age infants (AGA, n = 61) at birth to explore SGA related epigenome-wide DNA methylation sites. Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) was used to detect their umbilical cord blood Cu levels. Multiple linear regression models were used to explore the effect of Cu on SGA-related DNA methylation sites, and mediation analysis was further applied to explore the potential mediating factors of DNA methylation. The false discovery rate（FDR）was used for multiple comparisons.

Results

Compared with AGA (452 ng/mL), SGA infants (532 ng/mL) had higher umbilical cord blood Cu concentration (P < 0.05). Seven Cu-related CpG sites were identified from epigenome-wide DNA methylation association analysis with SGA. Among them, a significant mediation effect of FLT3（cg10763141） methylation level in the association between high exposure level of Cu and SGA (P = 0.024). The mediation analysis showed a mediation proportion of 44.7 %.

Conclusions

Consistent with previous findings, we found that Cu was associated with the risk of SGA, and seven differentially methylated sites significantly associated with Cu were observed in the epigenome wide DNA methylation association study of SGA. FLT3（cg10763141）mediates the correlation between Cu and SGA. Cu may increase the risk of SGA by altering DNA methylation in certain genes (particularly FLT3). Our study provides new clues for the mechanism of SGA.

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来源期刊

Journal of Trace Elements in Medicine and Biology 医学-内分泌学与代谢

CiteScore

6.60

自引率

2.90%

发文量

202

审稿时长

85 days

期刊介绍： The journal provides the reader with a thorough description of theoretical and applied aspects of trace elements in medicine and biology and is devoted to the advancement of scientific knowledge about trace elements and trace element species. Trace elements play essential roles in the maintenance of physiological processes. During the last decades there has been a great deal of scientific investigation about the function and binding of trace elements. The Journal of Trace Elements in Medicine and Biology focuses on the description and dissemination of scientific results concerning the role of trace elements with respect to their mode of action in health and disease and nutritional importance. Progress in the knowledge of the biological role of trace elements depends, however, on advances in trace elements chemistry. Thus the Journal of Trace Elements in Medicine and Biology will include only those papers that base their results on proven analytical methods. Also, we only publish those articles in which the quality assurance regarding the execution of experiments and achievement of results is guaranteed.