Our results showed that genetic variation in gene POU3F2 regulated gene expressions in dopaminergic synapse and AMPK pathways via methylations of POU3F2, KIF4B and TMSL3, which in turn influences CHL/HDL Ration, and finally led to AD and T2DM (Fig. 4A). This evidence concerns the gene TMSB4XP8 and type 2 diabetes mellitus.