MTHFR and type 2 diabetes mellitus: T2DM, SAH, Hcy levels, aging, smoking, and sedentary lifestyle exert epigenetic effects on DNA methylation and chromatin remodeling, histone acetylation, and microRNA expression and regulation.36,37 The reduced enzyme activity associated with the MTHFR 677C>T variant has been linked to decreased DNA methylation38 and HHcy.39 In turn, decreased DNA methylation may involve aberrant expression of structural and matrix proteins or reduced DNA integrity, resulting in premature aging of the vascular tissue.40