"A positive family history remains the most important independent risk factor for developing CD to date  . More recently, genome-wide analysis studies have revealed more than 30 loci associated with CD   . Of significance may be the genetic polymorphisms that alter adaptive immunity and the mutations associated with inadequate surveillance of bacteria by the intestinal mucosa     . "
[Show abstract][Hide abstract] ABSTRACT: Crohn's disease (CD) is an inflammatory disorder of the gastrointestinal tract that is likely caused by an inappropriate mucosal inflammatory response to intestinal bacteria in a genetically predisposed host. The lesions of CD can involve any region of the GI tract as well as extraintestinal sites such as the skin, joints, and eyes. The most common presenting symptoms are abdominal pain and prolonged diarrhea associated with fevers, fatigue, and malaise. Delayed growth and failure to thrive may also be observed in pediatric patients. Oral manifestations of CD are known as oral CD and may precede GI involvement, thus serving as early markers of this condition. We describe a 6-year-old male who presented with oral lesions as his initial manifestation of disease and review the current literature pertaining to oral CD.
"Although the nature and anatomical location of the inflammatory pathology differ between the two disorders, it is thought that both arise as a result of an abnormal immune response to the intestinal microbiota in genetically predisposed individuals. In Crohn's disease inflammation is transmural, can be granulomatous, and occurs in any part of the gastrointestinal tract although the ileum is mainly affected, whereas in ulcerative colitis, the pathology impacts primarily the colonic mucosa (Podolsky, 2002). Since the 1940s, the incidence of IBD has dramatically increased in countries with a more ''westernized'' lifestyle, suggesting the influence of environmental factors, including lifestyle, hygiene, diet, and use of antibiotics, all of which may alter the microbiota in favor of disease onset and/or progression (Shanahan and Bernstein, 2009). "
"The etiology of IBD most likely involves a complex interaction of genetic and environmental factors. Although the etiology remains poorly understood, epidemiologic and linkage studies suggest that genetic factors are implicated in the pathogenesis of IBD [3-9]. "
[Show abstract][Hide abstract] ABSTRACT: Polymorphisms in immunity-related GTPase family M (IRGM) gene may be associated with inflammatory bowel disease (IBD) by affecting autophagy. However, the genetic association studies on three common variants in IRGM gene (rs13361189, rs4958847 and rs10065172) have shown inconsistent results.
The PubMed and Embase were searched up to June 5, 2013 for studies on the association between three IRGM polymorphisms and IBD risk. Data were extracted and the odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Finally, we performed a meta-analysis of 25 eligible studies in 3 SNPs located at IRGM gene by using a total of 20590 IBD cases and 27670 controls. The analysis showed modest significant association for the rs13361189, rs4958847 and rs10065172 variants in Crohn's disease (CD): the risk estimates for the allele contrast were OR=1.306 (1.200-1.420), p=5.2×10(-10), OR=1.182 (1.082-1.290), p=0.0002, and OR=1.248 (1.057-1.473), p=0.009 respectively (still significant when the p value was Bonferroni adjusted to 0.017). When stratified by ethnicity, significantly increased CD risk was observed in Europeans, but not in Asians. Conversely, there was no association of rs13361189 or rs4958847 variant with risk of ulcerative colitis (UC).
These results indicated that autophagy gene-IRGM polymorphisms appear to confer susceptibility to CD but not UC, especially in Europeans. Our data may provide further understanding of the role of autophagy in the pathogenesis of CD.
PLoS ONE 11/2013; 8(11):e80602. DOI:10.1371/journal.pone.0080602 · 3.23 Impact Factor
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