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Sample Preparation to Bioinformatics Analysis of DNA Methylation: Association Strategy for Obesity and Related Trait Studies
Published on: May 6, 2022
DNA methylation of microRNA-375 in impaired glucose tolerance
Xiaoli Wang1, Xiangyun Chang1, Jun Li1
1Departments of Endocrinology and Metabolism, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, P.R. China.
Abstract:
In the present study, the expression levels and DNA methylation status of microRNA (miRNA)-375 in patients with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) were analyzed and the role of DNA methylation of miRNA-375 in the pathogenesis of T2DM was investigated. Compared with the miR-375 levels in patients with normal glucose tolerance (NGT; n=53), the samples from patients with IGT (n=44) exhibited downregulation of miR-375, while those from patients with T2DM (n=54) exhibited upregulation of miR-375 in the plasma. Additionally, the samples from patients with IGT were observed to be hypermethylated compared with those from patients with T2DM and NGT (P=0.042). Analysis of three CpG units (CpG1.2, CpG20 and CpG25.26.27) from 17 CpG sites (between -990 and -1,258 bp, relative to the transcription start site) revealed higher methylation levels in patients with IGT compared with those in patients with NGT (P<0.05). The methylation of two CpG units (CpG1.2 and CpG25.26.27) was higher in patients with IGT than in the patients with T2DM (P<0.05). Thus, the present study demonstrated that the miR-375 promoter was hypermethylated and the levels of miR-375 in the plasma were downregulated in the patients with IGT. DNA hypomethylation may have an important role in the regulation of miR-375 expression and may contribute to the pathogenesis of T2DM.
Insights
microRNA-375 (miRNA-375) levels and DNA methylation were analyzed in normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) patients. IGT patients showed downregulated miRNA-375 and hypermethylation, suggesting a role in T2DM pathogenesis.
Area of Science:
- Molecular Biology
- Endocrinology
- Epigenetics
Background:
- MicroRNAs (miRNAs) play crucial roles in regulating gene expression.
- Aberrant miRNA expression and epigenetic modifications are implicated in metabolic disorders like type 2 diabetes mellitus (T2DM).
- The specific role of miRNA-375 (miR-375) in glucose tolerance and T2DM pathogenesis requires further investigation.
Purpose of the Study:
- To analyze the expression levels and DNA methylation status of miR-375 in patients with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM.
- To investigate the potential role of miR-375 DNA methylation in the pathogenesis of T2DM.
Main Methods:
- Plasma samples were collected from patients diagnosed with NGT, IGT, and T2DM.
- Expression levels of miR-375 were quantified using appropriate molecular assays.
- DNA methylation status of the miR-375 promoter region, including specific CpG units, was analyzed.
Main Results:
- Plasma miR-375 levels were downregulated in IGT patients and upregulated in T2DM patients compared to NGT controls.
- Significant hypermethylation of the miR-375 promoter was observed in IGT patients compared to both NGT and T2DM patients.
- Specific CpG units within the miR-375 promoter showed increased methylation in IGT patients, correlating with downregulated miR-375 expression.
Conclusions:
- The study demonstrates that miR-375 promoter hypermethylation is associated with downregulated plasma miR-375 levels in patients with IGT.
- DNA hypomethylation of miR-375 may play a role in regulating its expression and potentially contribute to the pathogenesis of T2DM.
- These findings highlight the epigenetic regulation of miR-375 as a potential factor in glucose metabolism disturbances.
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