Abstract
Marfan syndrome (MFS) is a genetic disorder primarily affecting the connective tissue, with cardiovascular complications as the leading cause of mortality. While mutations in the FBN1 gene are the primary cause, the severity and progression of the disease can vary significantly among individuals. DNA methylation, a key epigenetic regulatory mechanism, has garnered attention in MFS research, particularly regarding methylation changes in the FBN1 locus and their effects on fibrillin-1 expression. Differential methylation and expression of genes related to inflammation (e.g., interleukin (IL)-10, IL-17) and oxidative stress (e.g., PON2, TP53INP1) have been linked to MFS aortic pathology. These alterations likely contribute to disease progression by influencing inflammatory responses, smooth muscle cell apoptosis, and biomechanical properties of the aorta. The transforming growth factor-beta (TGF-β) signaling pathway plays a central role in MFS pathology, with aberrant methylation of related genes potentially elevating active TGF-β levels and exacerbating aortic lesions. Notably, tissue-specific methylation patterns, especially in smooth muscle cells of the aorta, remain poorly understood. A deeper understanding of DNA methylation's role in MFS could pave the way for early interventions and epigenetic-targeted therapies.