Genetic variations in the autophagic pathway influence genetic predispositions to Crohn disease. Autophagy, the major lysosomal pathway for degrading and recycling cytoplasmic material, constitutes an important homeostatic cellular process. Of interest, single-nucleotide polymorphisms in ATG16L1 (autophagy-related 16-like 1 [S. cerevisiae]), a key component in the autophagic response to invading pathogens, have been associated with an increased risk of developing Crohn disease. The most common and well-studied genetic variant of ATG16L1 (rs2241880; leading to a T300A conversion) exhibits a strong association with risk for developing Crohn disease. The rs2241880 variant plays a crucial role in pathogen clearance, resulting in imbalanced cytokine production, and is linked to other biological processes, such as the endoplasmic reticulum stress/unfolded protein response. In this review, we focus on the importance of ATG16L1 and its genetic variant (T300A) within the elementary biological processes linked to Crohn disease.
Keywords: ATG16L1; ATG16L1, autophagy-related 16-like 1 (S. cerevisiae); BCL2, B-cell CLL/lymphoma 2; Crohn disease; DCs, dendritic cells; ER, endoplasmic reticulum; GWAS, genome-wide association studies; IBD, inflammatory bowel disease; MDP, muramyl dipeptide; MTOR, mechanistic target of rapamycin; NFKB, nuclear factor of kappa light polypeptide gene enhancer in B-cells; NOD2; NOD2, nucleotide-binding oligomerization domain containing 2; RIPK2, receptor-interacting serine-threonine kinase 2; SNP, single-nucleotide polymorphism; T300A, threonine-to-alanine substitution at amino acid position 300; TNF/TNF-α, tumor necrosis factor; UC, ulcerative colitis; ULK1, unc-51 like autophagy-activating kinase 1; XBP1, X-box binding protein 1; autophagy; bacterial clearance; endoplasmic reticulum stress.