title: Cannabinoid Receptor 2 Functional Variant Contributes to the Risk for Pediatric Inflammatory Bowel Disease.
abstract: We conducted a case-control association analysis to establish the role of a common CB2 functional variant, Q63R, in the susceptibility to inflammatory bowel disease (IBD).
  
  
  
  Endocannabinoids may limit intestinal inflammation through cannabinoid receptor 1 and/or 2 (CB1, CB2).
  
  
  
  We genotyped 217 pediatric IBD patients [112 Crohn's disease (CD), 105 ulcerative colitis (UC)] and 600 controls for the CB2-Q63R variant by Taqman assay. Data were collected from clinical records on age at diagnosis, disease activity, duration and location, extraintestinal manifestations, therapy, clinical relapses, and need for surgery.
  
  
  
  We found a significant association of the CB2-R63 variant with IBD (allele frequencies, P=0.04; genotype distributions, P=0.0006), in particular with CD (allele frequencies, P=0.002; genotype distributions, P=0.00005) and with UC only for genotype distributions (P=0.03). RR carriers showed an increased risk for developing IBD [odds ratio (OR)=1.82; P=0.0002 for IBD; OR=2.02; P=10 for CD; OR=1.63; P=0.02 for UC at 95% confidence interval]. Upon genotype-phenotype evaluation, RR patients showed an increased frequency of moderate-to-severe disease activity at diagnosis in the case of both CD and UC (P=0.01 and P=0.02, respectively) and also an earlier clinical relapse in UC (P=0.04). In UC, all the clinical features related to the CB2 risk allele were still significantly associated with the variant when analyzed using a multivariate logistic regression model (P=0.001).
  
  
  
  The CB2-Q63R variant contributes to the risk for pediatric IBD, in particular CD. The R63 variant is associated with a more severe phenotype in both UC and CD. Taken together, our data point toward the involvement of the CB2 receptor in the pathogenesis and clinical features of pediatric IBD.
authors.affiliation: Departments of Women, Child and General and Specialist Surgery.
authors.forename: Caterina
authors.initials: C
authors.lastname: Strisciuglio
authors.affiliation: Experimental Medicine, Division of Pharmacology "Leonardo Donatelli," The Second University of Naples.
authors.forename: Giulia
authors.initials: G
authors.lastname: Bellini
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II," Naples, Italy.
authors.forename: Erasmo
authors.initials: E
authors.lastname: Miele
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II," Naples, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Martinelli
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II," Naples, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Cenni
authors.affiliation: Experimental Medicine, Division of Pharmacology "Leonardo Donatelli," The Second University of Naples.
authors.forename: Chiara
authors.initials: C
authors.lastname: Tortora
authors.affiliation: Departments of Women, Child and General and Specialist Surgery.
authors.forename: Carlo
authors.initials: C
authors.lastname: Tolone
authors.affiliation: Departments of Women, Child and General and Specialist Surgery.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Miraglia Del Giudice
authors.affiliation: Departments of Women, Child and General and Specialist Surgery.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rossi
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D003093:Colitis, Ulcerative / Q000453:epidemiology* / Q000235:genetics / Q000503:physiopathology; D003424:Crohn Disease / Q000453:epidemiology* / Q000235:genetics / Q000503:physiopathology; D063388:Endocannabinoids / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics*; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: C588309:CNR2 protein, human; D063388:Endocannabinoids; D043885:Receptor, Cannabinoid, CB2