The ATG genes code for a protein complex that forms the autophagosome wall. If a patient cannot correctly develop an autophagosome, the lysosome needed to degrade the cellular waste cannot merge with the autophagosome. This leads to improper degradation of cellular debris and poor autophagy function.
All three of these genes play a significant role in autophagy, and a heterozygous or homozygous SNP will decrease a patient’s autophagy status. Typically, these patients do not deliver glucose well. They may be referred to as “Hangry”. Insulin resistance spurs an increase in mTOR, which can slow down autophagy, increasing cellular waste.
Central insulin signaling and the regulation of autophagy are relevant to a host of diverse disorders. Studies show that autophagy can increase with the increase of glucose concentration in the cell.
ATG5 / SNPs in the ATG5 gene have been associated with numerous neurological, immunological, and endocrine syndromes. Whereas, ATG5 alleles have been associated with blood pressure, insulin sensitivity, glucose homeostasis, and age-related macular degeneration.
ATG12 / ATG12 is specifically involved in turning off the innate immune response. Mutations in the ATG12 gene are predicted to lead to increased biological immune response activity and overall inflammation. Studies suggest that the significant roles of autophagy in the immune system include eliminating microbes, controlling inflammation, lymphocyte homeostasis, and the secretion of immune mediators.
ATG16L / The autophagy process plays a role within the intestinal epithelium. Mutations in the ATG16L1 gene have been associated with gastrointestinal disorders such as inflammatory bowel-related diseases. Due to inadequate glucose delivery, you may also see an increased predisposition for DM Type 2 and fatty liver disease in these patients.