title: Autophagy genes variants and paediatric Crohn's disease phenotype: a single-centre experience.
abstract: OBJECTIVE
  Little evidence demonstrating the correlation between several single nucleotide polymorphisms and a specific phenotype of Crohn's disease has been reported in children. We investigated the relationship between autophagy genes variants and clinical features in our children with Crohn's disease.
  
  
  METHODS
  Genotyping for ATG16L1, NOD2/CARD15, and IRGM1 was performed in 80 consecutive patients with Crohn's disease (median age: 11 years; range: 0.7-17.9 years). Crohn's disease location and behaviour were classified using the Paris classification. Additional data were collected from clinical records on patients' demographics, age at symptom onset and diagnosis, extraintestinal manifestations, therapy, clinical relapses, and need of surgical intervention.
  
  
  RESULTS
  Patients homozygous for the risk allele ATG16L1 (T300A) showed a trend towards switching to a stricturing phenotype during the course of disease compared to children either homozygous for the wild-type allele or heterozygous for the ATG16L1 single nucleotide polymorphism (p=0.01). Homozygosity for the ATG16L1 risk allele was associated with a major recurrence of clinical relapses and earlier introduction of immunosuppressants (p=0.006 and p=0.04, respectively). Heterozygosity for the NOD2 rs2066847 allele was associated with major ileal involvement (p=0.01).
  
  
  CONCLUSIONS
  In patients carrying the T300A variant, Crohn's disease follows a more aggressive clinical course.
authors.affiliation: Department of Translational Medical Sciences, Section of Pediatrics, University of Naples "Federico II", Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Strisciuglio
authors.affiliation: Department of Translational Medical Sciences, Section of Pediatrics, University of Naples "Federico II", Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: Auricchio
authors.affiliation: Department of Translational Medical Sciences, Section of Pediatrics, University of Naples "Federico II", Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Martinelli
authors.affiliation: Department of Translational Medical Sciences, Section of Pediatrics, University of Naples "Federico II", Italy. Electronic address: staiano@unina.it.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Staiano
authors.affiliation: Department of Translational Medical Sciences, Section of Pediatrics, University of Naples "Federico II", Italy.
authors.forename: Francesca Paola
authors.initials: FP
authors.lastname: Giugliano
authors.affiliation: Department of Translational Medical Sciences, Section of Pediatrics, University of Naples "Federico II", Italy.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Andreozzi
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology and CEINGE, University of Naples "Federico II", Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: De Rosa
authors.affiliation: Department of Translational Medical Sciences, Section of Pediatrics, University of Naples "Federico II", Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Giannetti
authors.affiliation: Department of Translational Medical Sciences, Section of Pediatrics, University of Naples "Federico II", Italy; Institute of Protein Biochemistry-CNR, Naples, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Gianfrani
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology and CEINGE, University of Naples "Federico II", Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Izzo
authors.affiliation: Department of Translational Medical Sciences, Section of Pediatrics, University of Naples "Federico II", Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Troncone
authors.affiliation: Department of Translational Medical Sciences, Section of Pediatrics, University of Naples "Federico II", Italy.
authors.forename: Erasmo
authors.initials: E
authors.lastname: Miele
mesh_terms: D000293:Adolescent; D001343:Autophagy / Q000235:genetics*; D000071183:Autophagy-Related Proteins; D002097:C-Reactive Protein / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003251:Constriction, Pathologic / Q000235:genetics; D003424:Crohn Disease / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005243:Feces / Q000737:chemistry; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007079:Ileitis / Q000235:genetics*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D012720:Severity of Illness Index
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D007166:Immunosuppressive Agents; D039841:Leukocyte L1 Antigen Complex; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D002097:C-Reactive Protein; D019204:GTP-Binding Proteins; C513539:IRGM protein, human
keywords: Autophagy; Crohn's disease; Genome wide association studies; Inflammatory bowel diseases