G-quadruplex formation in GCK and TM6SF2 are targets for differential DNA methylation in metabolic dysfunction-associated fatty liver disease and type II diabetes mellitus patients.

A preprint abstract from biorxiv.org discusses the interplay of environmental and genetic factors in metabolic diseases (MetDs) and their association with an increased risk of cancer. The study focuses on DNA methylation patterns in non-canonical DNA structures, such as G-quadruplexes or R-loops, in two MetD risk genes, GCK and TM6SF2. The researchers found significant differential methylation in these genes in MetD patients compared to healthy controls, and confirmed the formation of G-quadruplex structures in these regions. The study suggests that the elevated blood glucose and fatty acid levels in MetD patients could lead to changes in the non-B DNA landscape, causing differential methylation and altered transcription factor binding. The findings provide new insights into the mechanisms underlying MetDs and their link to cancer, and suggest that non-B DNA structures could be potential targets for therapeutic interventions. [Extracted from the article]