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

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.