Sara Rufini1, Cinzia Ciccacci2, Davide Di Fusco2, Alessandra Ruffa3, Francesco Pallone3, Giuseppe Novelli2, Livia Biancone3, Paola Borgiani2. 1. Department of Biomedicine and Prevention, Genetics Section, University of Rome "Tor Vergata", Italy. Electronic address: sara.rufini@hotmail.it. 2. Department of Biomedicine and Prevention, Genetics Section, University of Rome "Tor Vergata", Italy. 3. Gastroenterology Unit, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.
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.
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 diseasespatients 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 colitispatients 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 IRGMrs13361189 and rs4958847 polymorphisms to be important for Crohn's disease susceptibility and phenotype modulation, in accordance with previous findings.
Authors: Teminioluwa A Ajayi; Cynthia L Innes; Sara A Grimm; Prashant Rai; Ryan Finethy; Jörn Coers; Xuting Wang; Douglas A Bell; John A McGrath; Shepherd H Schurman; Michael B Fessler Journal: Am J Physiol Gastrointest Liver Physiol Date: 2018-10-18 Impact factor: 4.052
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