For instance, in a study by Peng et al. (2015), where subgroup analysis was based on APOE ε4 status, MTHFR C677T polymorphism was found to be only associated with the risk of AD in APOE ε4 carriers, but not in APOE ε4 non-carriers, indicating a synergic effect between MTHFR C677T polymorphism and the APOE ε4 allele. This evidence concerns the gene APOE and Alzheimer disease.