Hamdan Hamdan Z
Department of Pathology, College of Medicine, Qassim University, Buraidah, Saudi Arabia.
Int J Health Sci (Qassim). 2025 Mar-Apr;19(2):4-16.
Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder that adversely affects pregnant women and their growing fetuses. Evidence suggests that genetic and epigenetic modifications, such as DNA methylation, may contribute to the disease phenotype. This study aimed to identify GDM-related hub-methylated genes involved in GDM pathogenesis.
RNA-seq transcriptomic-wide data (GSE203346) and microarray epigenomic-wide data (GSE106099) were obtained from the Gene Expression Omnibus. Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression (DEGs) analysis were performed on the RNA-seq data using the "R" packages "WGCNA" and "DESeq2," respectively. Differentially methylated genes (DMGs) were identified using the "limma" package.
WGCNA identified 18 modules, with only two modules [MEyellow r = -0.32; = 0.042 and MEmagenta r = -0.32; = 0.041] showing significant inverse correlations with GDM and one module [MEblue r = 0.35; = 0.026], showing a direct correlation. Following intersecting the hub genes from WGCNA, DEGs and DMGs, six hub genes were identified as hypomethylated and highly expressed (UCKL1, SHANK2, GDPD5, CMYA5, ESRRG, NOS3), while two genes (DPYSL3 and FTH1) were hypermethylated and showed low expression. Gene set enrichment analysis revealed that the GDM-related hub DMGs were mainly enriched in pathways related to ferroptosis, VEGF signaling, and arginine and proline metabolism.
This multi-omics study identified eight novel GDM-related hub DMGs in placental tissue from GDM cases, suggesting their potential involvement in GDM pathogenesis. Further study is needed.
妊娠期糖尿病（GDM）是一种常见的代谢紊乱疾病，对孕妇及其发育中的胎儿产生不利影响。有证据表明，遗传和表观遗传修饰，如DNA甲基化，可能导致该疾病的表型。本研究旨在鉴定参与GDM发病机制的与GDM相关的关键甲基化基因。
从基因表达综合数据库获取RNA测序全转录组数据（GSE203346）和微阵列全表观基因组数据（GSE106099）。分别使用“R”包“WGCNA”和“DESeq2”对RNA测序数据进行加权基因共表达网络分析（WGCNA）和差异基因表达（DEG）分析。使用“limma”包鉴定差异甲基化基因（DMG）。
WGCNA鉴定出18个模块，其中只有两个模块[ME黄色r = -0.32；P = 0.042和ME品红色r = -0.32；P = 0.041]与GDM呈显著负相关，一个模块[ME蓝色r = 0.35；P = 0.026]呈正相关。在将WGCNA、DEG和DMG的中心基因进行交叉分析后，鉴定出6个低甲基化且高表达的中心基因（UCKL1、SHANK2、GDPD5、CMYA5、ESRRG、NOS3），而两个基因（DPYSL3和FTH1）高甲基化且低表达。基因集富集分析显示，与GDM相关的关键DMG主要富集在与铁死亡、VEGF信号传导以及精氨酸和脯氨酸代谢相关的途径中。
这项多组学研究在GDM病例的胎盘组织中鉴定出8个新的与GDM相关的关键DMG，表明它们可能参与GDM的发病机制。需要进一步研究。
