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    Exploring Differentially Methylated Genes among Preterm Birth and Full-Term Birth

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    Date
    2025-01-02
    Author
    Razzaq, Aleem
    ElKahlout, Razan
    Nasrallah, Gheyath K.
    Ibrahim, Faisal E.
    Samara, Muthanna
    Zayed, Hatem
    Abdulrouf, Palli Valapila
    Al-Jurf, Rana
    Najjar, Ahmed
    Farrell, Thomas
    Qoronfleh, M. Walid
    Rifai, Hilal Al
    Al-Dewik, Nader
    ...show more authors ...show less authors
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    Abstract
    INTRODUCTION: Preterm birth (PTB) is a major contributor to neonatal morbidity and mortality. DNA methylation plays a critical role in fetal development and may serve as an epigenetic biomarker for PTB. However, few epigenetic studies have investigated PTB-specific DNA methylation changes. This study aimed to identify epigenetic differences between PTB and term birth (TB) infants. METHODS: A total of 218 cord blood samples from three independent PTB studies were analyzed to identify epigenetic differences between PTB and TB infants. Differential methylation analysis was conducted while adjusting for key covariates, including gestational age, sex, and disease status. Differentially methylated regions (DMRs) (genes and promoters) and differentially methylated sites (DMSs) (CpG sites) were assessed for significant methylation differences between the two groups. RESULTS: In PTB infants, several genes, including RNASE3, HGF, CLEC5A, LIPN, NXF1, and CCDC12 showed significant hypermethylation (p < 0.05), while the MUC20 and IFNL4 genes showed significant hypomethylation (p < 0.05). The eForge analysis revealed that hypermethylated (p < 0.05) CpG sites were significantly enriched in different fetal tissues such as the small and large intestines, adrenal gland, fetal heart, lungs, and kidney, whereas hypomethylated CpGs showed no significant enrichment. Gene ontology analysis indicated that differentially methylated genes were primarily involved in immune response regulation. Notably, S100A9 and S100A8 genes, which play crucial roles in neonatal immune function and sepsis risk, were hypermethylated (p < 0.05) in PTB infants. CONCLUSION: This study identified PTB-associated DNA methylation changes in immune-related genes, suggesting their potential epigenetic biomarkers for PTB. These findings enhance our understanding of PTB pathogenesis and may contribute to the development of novel diagnostic and therapeutic strategies.
    URI
    https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=105006680746&origin=inward
    DOI/handle
    http://dx.doi.org/10.1159/000543372
    http://hdl.handle.net/10576/65565
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    • Biomedical Sciences [‎833‎ items ]

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