MTHFR and vitamin deficiency disorder: For example, some studies suggest a correlation between hyperhomocysteinemia and MTHFR promoter methylation [26]; others have linked MTHFR promoter methylation in blood cells with markers of chromosome damage, such as an increased frequency of micronuclei [27] or alterations of LINE-1 methylation and stability [15], and there is also indication that MTHFR promoter methylation in blood DNA might reflect dietary B-group vitamin deficiency [18,30] or environmental exposure to cancerous agents, such as those deriving from tobacco smoking [15].