title: NOD2 and ATG16L1 polymorphisms affect monocyte responses in Crohn's disease.
abstract: OBJECTIVE
  To assess whether polymorphisms in NOD2 and ATG16L1 affect cytokine responses and mycobacterium avium subspecies paratuberculosis (MAP) survival in monocytes from Crohn's disease (CD) patients.
  
  
  METHODS
  Monocytes were isolated from peripheral blood of CD patients of known genotype for common single nucleotide polymorphisms of NOD2 and ATG16L1. Monocytes were challenged with MAP and bacterial persistence assessed at subsequent time-points. Cytokine responses were assayed using a Milliplex multi-analyte profiling assay for 13 cytokines.
  
  
  RESULTS
  Monocytes heterozygous for a NOD2 polymorphism (R702W, P268S, or 1007fs) were more permissive for growth of MAP (P = 0.045) than those without. There was no effect of NOD2 genotype on subsequent cytokine expression. The T300A polymorphism of ATG16L1 did not affect growth of MAP in our model (P = 0.175), but did increase expression of cytokines interleukin (IL)-10 (P = 0.047) and IL-6 (P = 0.019).
  
  
  CONCLUSIONS
  CD-associated polymorphisms affected the elimination of MAP from ex vivo monocytes (NOD2), or expression of certain cytokines (ATG16L1), implying independent but contributory roles in the pathogenesis of CD.
authors: Department of Medicine, University of Chicago, IL 60637-1470, USA.
authors: Dylan M
authors: DM
authors: Glubb
authors: Richard B
authors: RB
authors: Gearry
authors: Murray L
authors: ML
authors: Barclay
authors: Rebecca L
authors: RL
authors: Roberts
authors: John
authors: J
authors: Pearson
authors: Jacqui I
authors: JI
authors: Keenan
authors: Judy
authors: J
authors: McKenzie
authors: Robert W
authors: RW
authors: Bentley
mesh_terms: D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D016207:Cytokines / Q000276:immunology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D016927:Mycobacterium avium subsp. paratuberculosis / Q000502:physiology; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D016207:Cytokines; D053473:Nod2 Signaling Adaptor Protein