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

Abstract

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.

• Authors: Sara Rufini, Cinzia Ciccacci, Davide Di Fusco, Alessandra Ruffa, Francesco Pallone, Giuseppe Novelli, Livia Biancone, Paola Borgiani
• Journal: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver (Dig Liver Dis) Vol. 47 Issue 9 Pg. 744-50 (Sep 2015) ISSN: 1878-3562 [Electronic] Netherlands
• PMID: 26066377 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Chemical References

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

Topics

• 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