The Expression Level of mRNA, Protein, and DNA Methylation Status of FOSL2 of Uyghur in XinJiang in Type 2 Diabetes

Abstract

Objective. We investigated the expression levels of both FOSL2 mRNA and protein as well as evaluating DNA methylation in the blood of type 2 diabetes mellitus (T2DM) Uyghur patients from Xinjiang. This study also evaluated whether FOSL2 gene expression had demonstrated any associations with clinical and biochemical indicators of T2DM. Methods. One hundred Uyghur subjects where divided into two groups, T2DM and nonimpaired glucose tolerance (NGT) groups. DNA methylation of FOSL2 was also analyzed by MassARRAY Spectrometry and methylation data of individual units were generated by the EpiTyper v1.0.5 software. The expression levels of FOS-like antigen 2 (FOSL2) and the protein expression levels were analyzed. Results. Significant differences were observed in mRNA and protein levels when compared with the NGT group, while methylation rates of eight CpG units within the FOSL2 gene were higher in the T2DM group. Methylation of CpG sites was found to inversely correlate with expression of other markers. Conclusions. Results show that a correlation between mRNA, protein, and DNA methylation of FOSL2 gene exists among T2DM patients from Uyghur. FOSL2 protein and mRNA were downregulated and the DNA became hypermethylated, all of which may be involved in T2DM pathogenesis in this population.

DNA methylation of candidate genes in peripheral blood from patients with type 2 diabetes or the metabolic syndrome

“…Several other genes, including CIDEP , FABP3 , FFAR , CCL2 and PRKCZ , have previously been identified to be differentially methylated in PBLs from diabetic patients[ 48 – 51 ] and could thus be of potential in the identification of metabolic diseases. Associations between altered levels of DNA methylation and gene expression were observed in T2D patients in several tissues, including PBL[ 13 , 16 , 51 , 52 ], which further supports the potential role of DNA methylation in metabolic diseases.…”

Increased expression of anion transporter SLC26A9 delays diabetes onset in cystic fibrosis

“…FOS TFs have been implicated in diabetes and glucose homeostasis. Computational analysis has suggested that FOS plays a role in the pathogenesis of T2D (77), and FOSL2 in T2D individuals has been shown to be hypermethylated, leading to lower mRNA and protein expression levels (78). Finally, we observed that TFs FOXA1, TFAP2A and 2C, and GATA3, which are known to be associated with type 2 diabetes risk (79), development, and subsequent maintenance of β cells (80) and insulin secretion (81), were absent in SLC26A9-expressing pancreatic cells in our study and in 2 of the 4 published studies (44,45).…”

The role of DNA methylation in the pathogenesis of type 2 diabetes mellitus

“…These findings indicate that Fosl2 expression plays a role in the positive regulation of insulin and glucose metabolism [ 29 ]. A detailed investigation into the blood DNA methylation status and expression level of the FOSL2 gene found that eight CpG units within the FOSL2 gene had higher methylation rates in T2DM patients, resulting in a significant reduction in FOSL2 mRNA and protein levels compared with normal glucose tolerance (NGT) group [ 31 ].…”