title: NOD2 mutations are associated with the development of intestinal failure in the absence of Crohn's disease.
abstract: OBJECTIVE
  Short bowel syndrome (SBS) and intestinal failure (IF) are multi-factorial conditions which in adults result from extensive intestinal resection. NOD2 is an intracellular pattern recognition receptor associated with CD. An unexpected high frequency of NOD2 mutations has been found in patients undergoing intestinal transplantation (35%). The role of NOD2 in a cohort with SBS/IF not specifically requiring intestinal transplantation has not been studied yet.
  
  
  METHODS
  The course of 85 patients with non-malignant SBS/IF was characterized. The major NOD2 mutations, as well as ATG16L1 and IL23R were determined. The allele frequencies were compared to the published frequencies of CD patients and controls.
  
  
  RESULTS
  In non-CD patients (72%) allele frequencies of NOD2 mutations were statistically more frequent than in controls (14% vs 6%, p = 0.006). In CD patients (28%) allele frequencies were not different between SBS and controls (29% vs 22%, p = 0.23). NOD2 mutations were neither associated with parameters potentially heralding the need for transplantation nor with an earlier time to the indication for intestinal transplantation.
  
  
  CONCLUSIONS
  NOD2 mutations are associated with the development of SBS/IF in the absence of CD, but not with specific complications. NOD2 mutations may increase the risk for more extensive intestinal resection or may impair intestinal adaptation.
authors.affiliation: 1st Medical Department, University of Tübingen, Germany; Department of Internal Medicine, Division of Gastroenterology and Endocrinology, University of Rostock, Ernst-Heydemann-Str. 6, 18057 Rostock, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Schäffler
authors.forename: Nina
authors.initials: N
authors.lastname: Schneider
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Hsieh
authors.forename: Johannes
authors.initials: J
authors.lastname: Reiner
authors.forename: Silvio
authors.initials: S
authors.lastname: Nadalin
authors.forename: Maria
authors.initials: M
authors.lastname: Witte
authors.forename: Alfred
authors.initials: A
authors.lastname: Königsrainer
authors.forename: Gunnar
authors.initials: G
authors.lastname: Blumenstock
authors.forename: Georg
authors.initials: G
authors.lastname: Lamprecht
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D015331:Cohort Studies; D003424:Crohn Disease / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007410:Intestinal Diseases / Q000235:genetics*; D007422:Intestines / Q000503:physiopathology / Q000637:transplantation; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000378:metabolism; D016331:Parenteral Nutrition, Home; D020641:Polymorphism, Single Nucleotide; D012778:Short Bowel Syndrome / Q000235:genetics*; D055815:Young Adult
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein
keywords: CD; Crohn's disease; HPN; IF; IFALD; Intestinal failure; Intestinal transplantation; NOD2; SBS; Short bowel syndrome; home parenteral nutrition; intestinal failure; intestinal failure associated liver disease; short bowel syndrome