title: A functional interleukin-10 mutation in Dutch patients with Crohn's disease.
abstract: OBJECTIVE
  Interleukin-10 is an anti-inflammatory and immunomodulatory cytokine. Interleukin-10 deficient mice are prone to develop chronic colitis. Administration of recombinant human interleukin-10 has been proposed to have a beneficial effect in a subgroup of patients with Crohn's disease. Recently, we found an interleukin-10 Gly15Arg mutation in a family with Crohn's disease which is associated with reduced interleukin-10 secretion by in vitro stimulated monocytes and lymphocytes. We hypothesised that this interleukin-10 mutation plays a role in maintaining the inflammatory process in Crohn's disease in some families.
  
  
  METHODS
  We evaluated interleukin-10 Gly15Arg in 379 patients with Crohn's disease, and 75 unrelated healthy controls. Also, first degree family members of interleukin-10 Gly15Arg carriers were evaluated. Additionally, mutation carriers and their relatives were evaluated for CARD15 R702W, G908R, and 1007fs.
  
  
  RESULTS
  Two patients with Crohn's disease were heterozygous for the interleukin-10 Gly15Arg mutation. No homozygotes were found. The Gly15Arg mutation was not observed in the controls. In first degree family members of the Crohn's disease-affected interleukin-10 Gly15Arg carriers, the mutation was found in Crohn's disease-affected as well as in their apparently healthy individuals. All family members carried one or two CARD15 mutation(s).
  
  
  CONCLUSIONS
  The interleukin-10 Gly15Arg mutation is rare in patients with Crohn's disease, and is not associated with the disease in the Netherlands.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: van der Linde
authors.forename: P P C
authors.initials: PP
authors.lastname: Boor
authors.forename: A A
authors.initials: AA
authors.lastname: van Bodegraven
authors.forename: D J
authors.initials: DJ
authors.lastname: de Jong
authors.forename: J B A
authors.initials: JB
authors.lastname: Crusius
authors.forename: T H J
authors.initials: TH
authors.lastname: Naber
authors.forename: E J
authors.initials: EJ
authors.lastname: Kuipers
authors.forename: J H P
authors.initials: JH
authors.lastname: Wilson
authors.forename: F W M
authors.initials: FW
authors.lastname: de Rooij
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005998:Glycine / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D053473:Nod2 Signaling Adaptor Protein; D017354:Point Mutation; D015183:Restriction Mapping
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D016753:Interleukin-10; D001120:Arginine; D005998:Glycine