Site-specific DNA methylation in KCNJ11 promoter contributes to type 2 diabetes

Abstract

AbstractAimsThis study explores the correlation between site-specific methylation levels of the KCNJ11 promoter and type 2 diabetes mellitus (T2DM), analyzing potential molecular mechanisms.MethodsThirty patients newly diagnosed with T2DM and 30 healthy controls were selected to determine the CpG methylation levels in the promoter region of the KCNJ11 gene using the bisulfite assay. The online software JASPAR was used to predict transcription factors binding to differentially methylated sites. Key transcription factors were further validated through quantitative PCR (q-PCR) and chromatin immunoprecipitation followed by PCR (ChIP-PCR).ResultsMethylation at multiple CpG sites within the KCNJ11 gene promoter was significantly reduced in newly diagnosed T2DM patients compared to healthy individuals. The methylation status of CpG-471, a site crucial for the binding of the transcription factor TCF12, emerged as potentially influential in T2DM pathogenesis. This reduction in methylation at CpG-471 may enhance TCF12 binding, thereby altering KCNJ11 expression.ConclusionHypomethylation of specific CpG sites in the promoter region of the KCNJ11 gene in patients with incipient T2DM potentially contributes to the disease’s pathogenesis. This hypomethylation enhances the transcriptional activity of TCF12, which binds to these sites, possibly influencing regulatory pathways involved in pancreatic beta-cell function.