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.

Rufini, S., Ciccacci, C., Di Fusco, D., Ruffa, A., Pallone, F., Novelli, G., et al. (2015). Autophagy and inflammatory bowel disease: Association between variants of the autophagy-related IRGM gene and susceptibility to Crohn's disease. DIGESTIVE AND LIVER DISEASE, 47(9), 744-750 [10.1016/j.dld.2015.05.012].

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

RUFINI, SARA;CICCACCI, CINZIA;PALLONE, FRANCESCO;NOVELLI, GIUSEPPE;BIANCONE, LIVIA;BORGIANI, PAOLA
2015-01-01

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.
2015
Pubblicato
Rilevanza internazionale
Articolo
Esperti non anonimi
Settore MED/12 - GASTROENTEROLOGIA
Settore MED/03 - GENETICA MEDICA
English
Autophagy; Genetics; IBD; Adult; Alleles; Autophagy; Case-Control Studies; Colitis, Ulcerative; Crohn Disease; Female; GTP-Binding Proteins; Genetic Predisposition to Disease; Humans; Italy; Male; Middle Aged; Nod2 Signaling Adaptor Protein; Phenotype; Polymorphism, Single Nucleotide; Young Adult; Gastroenterology; Hepatology; Medicine (all)
http://www.elsevier.com/wps/find/journalbibliographicinfo.cws_home/623449/description#bibliographicinfo
Rufini, S., Ciccacci, C., Di Fusco, D., Ruffa, A., Pallone, F., Novelli, G., et al. (2015). Autophagy and inflammatory bowel disease: Association between variants of the autophagy-related IRGM gene and susceptibility to Crohn's disease. DIGESTIVE AND LIVER DISEASE, 47(9), 744-750 [10.1016/j.dld.2015.05.012].
Rufini, S; Ciccacci, C; Di Fusco, D; Ruffa, A; Pallone, F; Novelli, G; Biancone, L; Borgiani, P
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
Autophagy and inflammatory bowel disease Association between variants of the autophagy-related IRGM gene and susceptibility to Crohn's disease.pdf

solo utenti autorizzati

Licenza: Copyright dell'editore
Dimensione 572.56 kB
Formato Adobe PDF
572.56 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/155327
Citazioni
  • ???jsp.display-item.citation.pmc??? 16
  • Scopus 33
  • ???jsp.display-item.citation.isi??? 30
social impact