In addition, hypermethylation of these specific genes (such as RASAL1, Klotho, etc.)can also directly lead to severe renal fibrosis, suggesting that the steady-state imbalance of DNA methylation directly affects renal fibrosis progression (Chen et al., 2013; Wing et al., 2014; Mao, 2015). The gene discussed is RASAL1; the disease is renal fibrosis.