How Can Molecules Induce Hemorrhoids? The Role of Genetics and Epigenetics in Hemorrhoidal Disease

The pathophysiology of hemorrhoids remains elusive; however, recent research has increasingly focused on the role of genetic and epigenetic mechanisms in this condition, offering prospects for targeted treatments. We conducted a review using PubMed, Embase, and Google Scholar, supplemented by citation searching, to summarize the current knowledge of the involvement of genetic and epigenetic mechanisms in hemorrhoids. Our review of 250 papers suggests that several genes, including FOXC2, NOX, NOS, and CALM3, may be responsible for the predisposing changes leading to the development of hemorrhoids. These genes have been associated with varicose veins, inflammation, and connective tissue alterations. Additionally, epigenetic mechanisms, particularly those mediated by miRNA, have been implicated in the clinical symptoms of hemorrhoids. While epigenetic regulation may influence inflammation, dilated vessels, and connective tissue degeneration, the exact mechanisms involved in these processes remain unclear. Furthermore, certain predisposing factors for hemorrhoids appear to involve both genetic and epigenetic mechanisms. This knowledge contributes to a better understanding of hemorrhoids and holds promise for developing novel therapeutic approaches.