Autophagy and inflammatory bowel disease: Association between variants of the autophagy-related IRGM gene and susceptibility to Crohn's disease. Issue 9 (September 2015)

• Record Type: Journal Article
• Authors: Rufini, Sara; Ciccacci, Cinzia; Di Fusco, Davide; Ruffa, Alessandra; Pallone, Francesco; Novelli, Giuseppe; Biancone, Livia; Borgiani, Paola
• Is Part Of: Digestive and liver disease. Volume 47:Issue 9(2015)
• Page Start: 744
• Page End: 750
• Publication Date: 2015-09
• Subjects: Digestive organs -- Diseases -- Periodicals; Liver -- Diseases -- Periodicals; 616.33005
• DOI: 10.1016/j.dld.2015.05.012
• Languages: English
• ISSNs: 1590-8658

Abstract

<abstract abstract-type="author" id="abs0005"> <title id="sect0005">Abstract</title> <sec> <title id="sect0010">Background</title> <p id="spar0005">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.</p> </sec> <sec> <title id="sect0015">Aims</title> <p id="spar0010">We analyzed known autophagic loci (<italic>IRGM</italic>, <italic>ULK1</italic> and <italic>AMBRA1</italic>) 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.</p> </sec> <sec> <title id="sect0020">Methods</title> <p id="spar0015">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.</p> </sec> <sec> <title id="sect0025">Results</title> <p id="spar0020"> <italic>IRGM</italic> was the most strongly associated with Crohn's disease susceptibility [rs13361189: <italic>P</italic> = 0.011, OR = 1.66 [95% CI: (1.12–2.45)]; rs4958847: <italic>P</italic> = 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 <italic>IRGM</italic> variants may modulate clinical characteristics of Crohn's disease.</p> </sec> <sec> <title id="sect0030">Conclusions</title> <p id="spar0025">Our study confirms <italic>IRGM</italic> rs13361189 and rs4958847 polymorphisms to be important for Crohn's disease susceptibility and phenotype modulation, in accordance with previous findings.</p> </sec> </abstract>