However, numerous studies conducted over three decades have suggested that chronic inappropriate increases in levels of local and circulating chemical mediators such as angiotensin II (Ang II) and endothelin-1 (ET-1) and fibrogenic cytokines/proteins such as transforming growth factor (TGF), connective tissue growth factor (CTGF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), and mast cell chymase and tryptase enzymes are likely to be key driving forces culminating in gingival overgrowth (Figure 1). This evidence concerns the gene CMA1 and gingival overgrowth.