scholarly journals Expression and DNA methylation status of microRNA-375 in patients with type 2 diabetes mellitus

2013 ◽  
Vol 9 (3) ◽  
pp. 967-972 ◽  
Author(s):  
KAN SUN ◽  
XIANGYUN CHANG ◽  
LIANG YIN ◽  
JUN LI ◽  
TING ZHOU ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Dna Methylation ◽  
Type 2 Diabetes Mellitus ◽  
Methylation Status

scholarly journals Epigenetic alterations in patients with type 2 diabetes mellitus

2015 ◽  
Vol 18 (2) ◽  
pp. 15-24 ◽  
Author(s):  
S Karachanak-Yankova ◽  
R Dimova ◽  
D Nikolova ◽  
D Nesheva ◽  
M Koprinarova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Dna Methylation ◽  
Type 2 Diabetes Mellitus ◽  
Methylation Status ◽  
Expression Levels ◽  
Stress Protection ◽  
Oxidative Stress Protection

Abstract Epigenetic changes, in particular DNA methylation processes, play a role in the pathogenesis and progression of type 2 diabetes mellitus (T2DM) linking genetic and environmental factors. To clarify this role, we have analyzed in patients with different duration of T2DM: (i) expression levels of methyl-CpG-binding domain protein 2 (MBD2) as marker of DNA methylation, and ii) methylation changes in 22 genes connected to cellular stress and toxicity. We have analyzed MBD2 mRNA expression levels in16 patients and 12 controls and the methylation status of stress and toxicity genes in four DNA pools: (i) controls; (ii) newly-diagnosed T2DM patients; (iii) patients with T2DM duration of <5 years and (iv) of >5 years. The MBD2 expression levels were 10.4-times increased on average in T2DM patients compared to controls. Consistent increase in DNA methylation fraction with the increase in T2DM duration was observed in Prdx2 and SCARA3 genes, connected to oxidative stress protection and in BRCA1 and Tp53 tumor-suppressor genes. In conclusion, increased MBD2 expression in patients indicated general dysregulation of DNA methylation in T2DM. The elevated methylation of Prdx2 and SCARA3 genes suggests disturbance in oxidative stress protection in T2DM. The increased methylation of BRCA1 and Tp53 genes unraveled an epigenetic cause for T2DM related increase in cancer risk.

scholarly journals Blood DNA methylation and type 2 diabetes mellitus

Medicine ◽  
2020 ◽  
Vol 99 (23) ◽  
pp. e20530
Author(s):  
Xian Wang ◽  
Jiao Yang ◽  
Xianliang Qiu ◽  
Qing Wen ◽  
Min Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Dna Methylation ◽  
Type 2 Diabetes Mellitus

scholarly journals Effect of He Qi San on DNA Methylation in Type 2 Diabetes Mellitus Patients with Phlegm-blood Stasis Syndrome

2019 ◽  
Vol 17 (1) ◽  
pp. 1213-1221
Author(s):  
Chu Shufang ◽  
Zhou Yinan ◽  
Li Huilin ◽  
Zhao Hengxia ◽  
Liu Deliang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Dna Methylation ◽  
Type 2 Diabetes Mellitus ◽  
Lipid Metabolism ◽  
Insulin Signaling ◽  
Blood Stasis ◽  
Blood Stasis Syndrome ◽  
Glucose And Lipid Metabolism

AbstractThis study was performed to elucidate the potential influence of He Qi San (HQS) on glucose and lipid metabolism in type 2 diabetes mellitus (T2DM) patients with phlegm-blood stasis syndrome (PBSS), and to determine DNA methylation changes. Sixty T2DM patients with PBSS were randomly divided into control and HQS groups. The control group received conventional treatments, and the HQS group received conventional treatments plus HQS. Glucose metabolism (FPG, 2hPG, FINS, and HbA1c) and lipid metabolism indexes (TG, TC and LDL-C) were determined. Genes with differential DNA methylation were subjected to GO and KEGG analyses. Glucose and lipid metabolism indexes in both groups were reduced, but were much more pronounced in the HQS group. Differential promoter CpG methylation regions were identified in 682 genes, including 426 genes with high-CpG promoters, 150 genes with intermediate CpG promoters, and 106 genes with low CpG promoters. Genes with differential DNA methylation were mainly enriched in the AMPK and insulin signaling pathways, terpenoid backbone biosynthesis, and renin secretion. We concluded that HQS remarkably improved indexes of glucose and lipid metabolism in T2DM patients with PBSS through regulating the DNA methylation of genes in the AMPK and insulin signaling pathways and terpenoid backbone biosynthesis.

scholarly journals Methylation status of vault RNA 2-1 promoter is a predictor of glycemic response to glucagon-like peptide-1 analog therapy in type 2 diabetes mellitus

2021 ◽  
Vol 9 (1) ◽  
pp. e001416
Author(s):  
Chia-Hung Lin ◽  
Yun-Shien Lee ◽  
Yu-Yao Huang ◽  
Chi-Neu Tsai
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Dna Methylation ◽  
Methylation Status ◽  
Training Group ◽  
Glycemic Response ◽  
Validation Group ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

IntroductionTherapeutic efficiency of glucagon-like peptide-1 (GLP-1) analog is about 50%–70% in type 2 diabetes mellitus (T2DM). Discovery of potential genetic biomarkers for prediction of treatment efficiency of GLP-1 analog before therapy is still necessary. We assess whether DNA methylation was associated with glycemic response to GLP-1 analog therapy in patients with poorly controlled T2DM.Research design and methodsGenomic DNA was extracted from the peripheral blood of training (n=10) and validation (n=128) groups of patients with T2DM receiving GLP-1 analogs. DNA methylome was analyzed using Infinium Human Methylation EPIC Bead Chip in the training group. The candidate genes were examined using a pyrosequencing platform in the validation group. The association between DNA methylation status and glycemic response to GLP-1 was analyzed in these patients.ResultsThe most differential methylation region between those with a good (responsive) and poor (unresponsive) glycemic response to GLP-1 analog therapy was located on chromosome 5q31.1 (135415693 to 135416613), the promoter of VTRNA2-1 in the training group. The methylation status of the VTRNA2-1 promoter was examined in the validation group via pyrosequencing reaction, and the hypomethylation of VTRNA2-1 (<40% methylation) was significantly associated with poor glycemic response to GLP-1 treatment (OR 2.757, 95% CI 1.240 to 6.130, p=0.011). Since the VTRNA2-1 promoter region was previously reported maternal imprinting extended to the adjacent centromeric CCCTC-binding factor site that contained an A/C polymorphism (rs2346018), which was associated with methylation density of VTRNA2-1, this A/C polymorphism was also integrated to analyze association with glycemic response to GLP-1 analog therapy. In patients with the A allele of rs2346018 and hypomethylation (<40%) on the VTRNA2-1 promoter, the OR increased to 4.048 (95% CI 1.438 to 11.389, p=0.007).ConclusionsThe glycemic response to GLP-1 analog treatment is associated with the methylation status of the VTRNA2-1 promoter and polymorphism of rs2346018.

scholarly journals Increased PARylation impacts the DNA methylation process in type 2 diabetes mellitus

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Michele Zampieri ◽  
Maria Giulia Bacalini ◽  
Ilaria Barchetta ◽  
Stefania Scalea ◽  
Flavia Agata Cimini ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Dna Methylation ◽  
Type 2 Diabetes Mellitus ◽  
Cytosine Methylation ◽  
Methylation Pattern ◽  
Post Translational Modification ◽  
Site Specific ◽  
Dna Methylation Pattern

Abstract Background Epigenetic modifications, such as DNA methylation, can influence the genetic susceptibility to type 2 diabetes mellitus (T2DM) and the progression of the disease. Our previous studies demonstrated that the regulation of the DNA methylation pattern involves the poly(ADP-ribosyl)ation (PARylation) process, a post-translational modification of proteins catalysed by the poly(ADP-ribose) polymerase (PARP) enzymes. Experimental data showed that the hyperactivation of PARylation is associated with impaired glucose metabolism and the development of T2DM. Aims of this case–control study were to investigate the association between PARylation and global and site-specific DNA methylation in T2DM and to evaluate metabolic correlates. Results Data were collected from 61 subjects affected by T2DM and 48 healthy individuals, recruited as controls. Global levels of poly(ADP-ribose) (PAR, a surrogate of PARP activity), cytosine methylation (5-methylcytosine, 5mC) and de-methylation intermediates 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC) were determined in peripheral blood cells by ELISA-based methodologies. Site-specific DNA methylation profiling of SOCS3, SREBF1 and TXNIP candidate genes was performed by mass spectrometry-based bisulfite sequencing, methyl-sensitive endonucleases digestion and by DNA immuno-precipitation. T2DM subjects presented higher PAR levels than controls. In T2DM individuals, increased PAR levels were significantly associated with higher HbA1c levels and the accumulation of the de-methylation intermediates 5hmC and 5fC in the genome. In addition, T2DM patients with higher PAR levels showed reduced methylation with increased 5hmC and 5fC levels in specific SOCS3 sites, up-regulated SOCS3 expression compared to both T2DM subjects with low PAR levels and controls. Conclusions This study demonstrates the activation of PARylation processes in patients with T2DM, particularly in those with poor glycaemic control. PARylation is linked to dysregulation of DNA methylation pattern via activation of the DNA de-methylation cascade and may be at the basis of the differential gene expression observed in presence of diabetes.

Sign in / Sign up

Export Citation Format

Share Document