Liver metabolism, GRAMD1A and ME

Germain et al found disturbances in fatty acid and lipid metablism in ME patients. The results were suggestive to damage to liver / a deficiency in liver activity (1).

de Vega et al showed that the most hypermethylated gene associated with quality of life in ME patients was GRAMD1A. A hypermethylated gene is often associated with supressed transcription (2).

GRAMD1A promotes the expansion of hepatocellular carcinoma stem cell and hepatocellular carcinoma growth through STAT5 (3).

If up-regulated GRAMD1A up-regulates STAT5 and induces growth in cancer cells, what do a down-regulated GRAMD1A do in ME patients? In liver cells? In lymphocytes?

STAT5 is involved in lymphocyte development and transformation. And STAT5 promotes the proliferation, survival and selfrenewal of hematopoietic stem cells (ref 21-24 in ref 3).

References:

1. Germain et al: Metabolic profiling of a ME/CFS discovery cohort reveals disturbances in fatty acid and lipid metabolism. Mol. BioSyst. 2017, 13, 371
2. Vega et al: Epigenetic modifications and glucocorticoid sensitivity in ME/CFS. BMC Medical Genomics, 2017, 10, 11
3. Binsheng Fu et al: GRAMD1A promotes the expansion of hepatocellular carcinoma stem cell and hepatocellular carcinoma growth through STAT5. Nature Scientific Reports, 2. sept 2016.