Exploring Differentially Methylated Genes amongst Preterm birth and Full-term birth.

IF 2 4区医学 Q3 GENETICS & HEREDITY

Lifestyle Genomics Pub Date : 2025-01-02 DOI:10.1159/000543372

Aleem Razzaq, Razan ElKahlout, Gheyath K Nasrallah, Faisal E Ibrahim, Muthanna Samara, Hatem Zayed, Palli Valapila Abdulrouf, Rana Al-Jurf, Ahmed Najjar, Thomas Farrell, M Walid Qoronfleh, Hilal Al Rifai, Nader Al-Dewik

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引用次数: 0

Abstract

Introduction: Preterm birth (PTB) is associated with newborn morbidity and mortality. DNA methylation plays an important role in the development of fetus, thus can also serve as an epigenetic biomarker. Limited epigenetic studies were conducted in regard to PTB. Thus, this study aims to determine whether there are any epigenetic changes amongst PTB vs. term birth (TB).

Methods: In the current study, a total 218 cord blood samples from three different PTB studies have been carried out to explore differentially methylated sites (DMS) and regions (DMRs) associated with PTB. The differential methylation analysis was done after controlling for multiple covariates like age, gender, and disease status. The DMRs (genes and promoters) and DMS (CpG) were investigated in PTB compared to TB infants.

Results: In PTB infants, genes like RNASE3, HGF, CLEC5A, LIPN, NXF1, and CCDC12 showed hypermethylation (p < 0.05) while the MUC20 and IFNL4 genes showed hypomethylation (p < 0.05) along with other significantly identified genes in this analysis. The eForge analysis of hypermethylated (p < 0.05) CpG sites exhibited enrichment in different fetal tissues like small and large intestine, adrenal gland, fetal heart, lungs, and kidney while hypomethylated CpGs showed no significant enrichment. The GO enrichment analysis of these genes revealed pathways associated with the regulation of immune response. Interestingly, the analysis also observed S100A9 and S100A8 genes, along with their associated CpG sites exhibited hypermethylation (p < 0.05) in PTB infants which plays a crucial role in developing neonatal sepsis.

Conclusion: Overall, this study revealed differential methylation in immune-related genes related to PTB that could be used as potential epigenetics biomarkers. These findings not only enhance our understanding of PTB pathogenesis but also pave the way for developing innovative diagnostic and therapeutic strategies.

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早产儿和足月新生儿甲基化基因差异的研究。

前言：早产（PTB）与新生儿发病率和死亡率相关。DNA甲基化在胎儿发育过程中起着重要的作用，因此也可以作为一种表观遗传生物标志物。对肺结核进行了有限的表观遗传学研究。因此，本研究旨在确定PTB与足月分娩（TB）之间是否存在任何表观遗传变化。方法：在目前的研究中，来自三个不同的PTB研究的总共218份脐带血样本进行了研究，以探索与PTB相关的差异甲基化位点（DMS）和区域（DMRs）。差异甲基化分析是在控制了年龄、性别和疾病状态等多个协变量后进行的。对PTB患儿的DMRs（基因和启动子）和DMS （CpG）进行了比较研究。结果：在PTB患儿中，RNASE3、HGF、CLEC5A、LIPN、NXF1、CCDC12等基因表现为高甲基化（p < 0.05）， MUC20、IFNL4等基因表现为低甲基化（p < 0.05）。eForge分析显示，高甲基化（p < 0.05）的CpG位点在小肠、大肠、肾上腺、胎儿心脏、肺和肾脏等不同的胎儿组织中都有富集，而低甲基化的CpG位点则没有显著富集。这些基因的氧化石墨烯富集分析揭示了与免疫反应调节相关的途径。有趣的是，该分析还观察到S100A9和S100A8基因及其相关的CpG位点在PTB婴儿中表现出高甲基化（p < 0.05），这在新生儿败血症的发生中起着至关重要的作用。结论：总体而言，本研究揭示了PTB相关免疫相关基因的差异甲基化，可作为潜在的表观遗传学生物标志物。这些发现不仅增强了我们对肺结核发病机制的理解，而且为开发创新的诊断和治疗策略铺平了道路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lifestyle Genomics Agricultural and Biological Sciences-Food Science

CiteScore

4.00

自引率

7.70%

发文量

审稿时长

28 weeks

期刊介绍： Lifestyle Genomics aims to provide a forum for highlighting new advances in the broad area of lifestyle-gene interactions and their influence on health and disease. The journal welcomes novel contributions that investigate how genetics may influence a person’s response to lifestyle factors, such as diet and nutrition, natural health products, physical activity, and sleep, amongst others. Additionally, contributions examining how lifestyle factors influence the expression/abundance of genes, proteins and metabolites in cell and animal models as well as in humans are also of interest. The journal will publish high-quality original research papers, brief research communications, reviews outlining timely advances in the field, and brief research methods pertaining to lifestyle genomics. It will also include a unique section under the heading “Market Place” presenting articles of companies active in the area of lifestyle genomics. Research articles will undergo rigorous scientific as well as statistical/bioinformatic review to ensure excellence.