Autophagy and inflammatory bowel disease: Association between variants of the autophagy-related IRGM gene and susceptibility to Crohn's disease

Dig Liver Dis. 2015 Sep;47(9):744-50. doi: 10.1016/j.dld.2015.05.012. Epub 2015 May 21.


Background: Crohn's disease and ulcerative colitis are inflammatory bowel diseases involving a genetically determined inappropriate mucosal immune response towards luminal antigens, including resident bacterial flora. Recent studies identified susceptibility genes involved in autophagy.

Aims: We analyzed known autophagic loci (IRGM, ULK1 and AMBRA1) previously described as associated with inflammatory bowel diseases or with other autoimmune and/or inflammatory disorders in a sample of Italian inflammatory bowel diseases patients in order to confirm their possible involvement and relative contribution in the disease.

Methods: We performed a case-control association study, a sub-phenotype correlation and a haplotype analysis. The analysis included 263 Crohn's disease, 206 ulcerative colitis patients and 245 matched healthy controls. Five polymorphisms were genotyped by allelic discrimination assays.

Results: IRGM was the most strongly associated with Crohn's disease susceptibility [rs13361189: P=0.011, OR=1.66 [95% CI: (1.12-2.45)]; rs4958847: P=0.05, OR=1.43 [95% CI: (1-2.03)]. The SNP rs13361189 was also found to increase the risk of Crohn's disease clinical sub-phenotype (fibrostricturing behaviour, ileal disease, perianal disease, intestinal resection). These findings suggest that IRGM variants may modulate clinical characteristics of Crohn's disease.

Conclusions: Our study confirms IRGM rs13361189 and rs4958847 polymorphisms to be important for Crohn's disease susceptibility and phenotype modulation, in accordance with previous findings.

Keywords: Autophagy; Genetics; IBD.

MeSH terms

  • Adult
  • Alleles
  • Autophagy / genetics*
  • Case-Control Studies
  • Colitis, Ulcerative / genetics*
  • Crohn Disease / genetics*
  • Female
  • GTP-Binding Proteins / genetics*
  • Genetic Predisposition to Disease
  • Humans
  • Italy
  • Male
  • Middle Aged
  • Nod2 Signaling Adaptor Protein / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Young Adult


  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • GTP-Binding Proteins
  • IRGM protein, human