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The supraphysiologic level of hepatic SAMe level in the Gnmt KO mice resulted in hypermethylation of the promoter regions of Ras and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) inhibitors (Ras-association domain family/tumor suppressor (RASSF) 1 and 4 and suppressor of cytokine signaling (SOCS) 13 and cytokine-inducible SH2-protein), resulting in decreased expression of these inhibitors and increased expression and activity of Ras and JAK/STAT pathways [37]