title: Autophagy 16-like 1 rs2241880 G allele is associated with Crohn's disease in German children.
abstract: OBJECTIVE
  Genome-wide association studies have described an association of the ATG16L1 (autophagy 16-like 1) gene rs2241880 variant with Crohn's disease (CD). Therefore, we evaluated this polymorphism in early-onset CD in 152 children and 253 controls and for the first time determined ATG16L1 colonic expression in German CD children.
  
  
  METHODS
  Investigation of rs2241880 allele frequencies using a predesigned single nucleotide polymorphism genotyping assay. Analysis of digenic epistasis between rs2241880 and the three common nucleotide-binding oligomerization domain containing two (NOD2/CARD15) mutations. Determination of ATG16L1 gene expression in large-bowel biopsies of selected patients and controls using real-time polymerase chain reaction.
  
  
  RESULTS
  The rs2241880G risk allele frequency was higher in CD compared with controls (63.0% vs. 47.4%; p = 0.0002). No epistasis between NOD2/CARD15 mutations and rs2241880 was observed; however, carriers of both variants had significantly increased disease risk. Transcriptional analysis did not reveal over- or underexpression of ATG16L1 in CD patients compared with controls.
  
  
  CONCLUSIONS
  We confirmed the association of CD with ATG16L1 rs2241880 variant in early-onset CD. As no epistatic interaction with three common NOD2/CARD15 mutations was observed, the p.Thr300Ala substitution is an independent risk factor for paediatric CD and supports the role for autophagy in disease pathogenesis.
authors: Department of Paediatric Surgery, Research Laboratories, University of Munich, Munich, Germany. martin.lacher@lmu.de
authors: Martin
authors: M
authors: Lacher
authors: Sebastian
authors: S
authors: Schroepf
authors: Antje
authors: A
authors: Ballauff
authors: Peter
authors: P
authors: Lohse
authors: Dietrich
authors: D
authors: von Schweinitz
authors: Roland
authors: R
authors: Kappler
authors: Sibylle
authors: S
authors: Koletzko
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000208:ethnology / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D055106:Genome-Wide Association Study; D005838:Genotype; D005858:Germany; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins