**9. Non-Genetic and Epigenetic Influences**

The relationship between *SCN5A* variants and the risk of DCM may be influenced by factors other than genotype. Studies of a DCM family carrying the loss-of-function A1180V variant demonstrated that the defective sodium channel reduced the current conduction (manifested as QRS widening) only at high heart rates [26]. These findings speak in favor of the fact that certain *SCN5A* variants might be risk factors of DCM, and that physical activity, lifestyle, and health conditions that increase the heart rate might enhance the phenotype of carriers of certain *SCN5A* variants, such as the A1180V [26]. Alternatively, epigenetic influences on NaV1.5 expression might influence the phenotype development, but this hypothesis requires further investigation.
